In February 2022, a 74-year-old woman was presented with a mass shadow in the lower lobe of her left lung during a periodic review after a breast cancer operation. (Figure 1A). This patient underwent a left mastectomy in September 2012 due to a malignant tumor in the left breast in another hospital. Postoperative pathology showed that the malignant tumor in the left breast was an invasive lobular carcinoma. Metastatic cancer was not found in lymph nodes and did not metastasize in pectoralis fibro-fatty tissue. Tumor cells appeared as cords and trabeculae with fibrous tissue hyperplasia (Supplementary Figure S1). A series of IHC results suggested ER (+), PR (-), HER2 (-), Ki-67 (+, 5%), E-cadherin (-), P120 (+), EGFR (-), CK5/6 (-), P63 (-), calponin (-), CK7 (+), CK20 (-), LCA (-), TTF-1 (-), HEP (-), GCDFP-15 (-), PAS (+), and AB (-). The patient was treated with six cycles of anthracycline drugs after surgery, and exemestane was prescribed until December 2021, during which the periodic review showed no abnormalities. The CT scan found a pulmonary nodule in the left lung until February 2022. The abnormal focus of the lung was on the left side of the body, which was the same as the breast lesions 9 years ago. PET-CT showed that the nodules in the left lower lobe of the lung were well demarcated and had morphological rules that were not typical of lung cancer (Figure 1B). On 4 March 2022, the left lower lobe tumor biopsy of the patient's lung showed poorly differentiated carcinoma (Figure 1C). The combined results of differential IHC detection for lung adenocarcinoma and squamous cell carcinoma suggested TTF-1 (-), napsin A (-), CK7 (+), p40 (-), and p63 (-). The results of IHC detection in the left lower lobe of the lung to analyze whether it originated from breast cancer suggested ER (-), PR (-), HER2 (-), Ki-67 (+, 15%), GCDFP-15 (-), and GATA-3 (-). The results of IHC detection in the left lower lobe of the lung to analyze whether it originated from intestinal cancer suggested CK20 (-), SATB2 (-), and CDX-2 (-). PD-L1 (22C3) showed a TPS<1%. Tumor markers were all in the normal range, including CA125, CEA, SCC, NSE, ProGRP, and CYFRA21-1. Practitioners considered not to exclude metastatic breast cancer through a combination of clinical history, IHC analysis, and imaging manifestations. Furthermore, PET-CT was implemented to understand the patient's general condition. Results showed that a malignant tumor is considered in the lower lobe of the left lung, and lymph node metastasis should be considered under the left pulmonary hilum (Figure 1B). There were no space-occupied lesions and abnormal metabolism of FDG in the postoperative area of left breast cancer. It was worth noting that PET-CT found a malignant space-occupying lesion in the initial segment of the ascending colon (Figure 2A). The subsequent colonoscopic biopsy revealed mucinous adenocarcinoma. IHC results suggested GATA-3 (-), mammaglobin (-), CDX-2 (+), SATB2 (+, individual cells are positive), GCDFP-15 (-), and HER2 (-). Pathological analysis after laparoscopically assisted right hemicolectomy confirmed mucinous adenocarcinoma of the colon again (Figure 2B). The pathological stage was pT2N0M0, which was different from the pathology of the left inferior pulmonary lobe. At this point, the origin of the malignant lung mass in this patient had not been determined after a pathological assessment of needle biopsy and imaging evaluation. A surgical pathology sample was needed to determine the origin of the tumor tissue, but the patient's chest structure showed no indications for surgery. We used two simultaneous approaches to identify the source of malignant tumors in the lower lobe of the left lung. The tissue traceability expression profile was initially detected in punctured tissue, and the details are provided in Supplementary Table S1. The results showed that the malignant tumor in the lower lobe of the left lung originated from breast cancer (Figure 3). The maximum tumor tissue similarity score was 100, and the results suggested that lung and colorectal cancer similarity scores were deficient, at only 0.7 and 1.9, respectively. It indicated that the lesion in the lower lobe of the left lung was not a primary pulmonary lesion and was not metastatic from the ascending colon. This was consistent with the pathological analysis results. The left lower lobe nodule was a poorly differentiated carcinoma, and the ascending colon nodule was a mucinous adenocarcinoma. There were no apparent standard features between the two lesions. The tissue traceability expression profile results exhibited essential reference values for subsequent diagnosis and treatment. Then, more than 600 hot spot exon regions and some intron regions of tumorigenesis and developmental genes were analyzed by NGS. DNA was extracted from plasma. The Illumina NextSeq 500 System (Illumina, San Diego, USA) was used for NGS. The average sequencing depth was at least x1,000. Unfortunately, no tumor-driving gene was found in this test. Only a somatic point mutation FAT1 p.G4570S was obtained, which has not been found in other studies and has not been recorded in COSMIC or other databases. Based on the comprehensive evaluation results, a malignant lung tumor in the left lower lobe was initially diagnosed as stage IV triple-negative cancer. After a multidisciplinary treatment (MDT) discussion, the patient was treated with C1-C4 paclitaxel albumin and capecitabine on 2022-4-7, 2022-4-29, 2022-5-24, and 2022-6-20. The specific regimen was planned with 1,500 mg orally twice daily on days 1-14 and 200 mg intravenous infusion of paclitaxel albumin on days 1 and 8. The radiotherapy plan was added on 22 July 2022, including 10 MV-X SAD 100 DT 214 cGy/F/d in the intensity-modulated field of the chest tumor area (including lesions in the lower left lung and mediastinal metastatic lymph nodes) and 10 MV-X SAD 100 DT 180 cGy/F/d in the intensity-modulated field of the high-risk chest area. She was scheduled to finish radiotherapy 28 times. Combined with the chemotherapy regimen, the specific regimen was provided with 1,500 mg orally twice daily and 190 mg intravenous infusion of paclitaxel albumin on days 1 and 8 (q3w). The longest diameter of the left lower pulmonary nodule narrowed from 29 mm to 14 mm in September 2022. A partial response (PR) was achieved, with lesion diameters decreasing by 51.72% (Figure 4). She is currently in stable condition.