Lymph node metastasis examined by the resected lymph nodes is considered one of the most important prognostic factors for colorectal cancer (CRC). However, it requires careful and comprehensive inspection by expert pathologists. To relieve the pathologists’ burden and speed up the diagnostic process, in this paper, we develop a deep learning system with the binary positive/negative labels of the lymph nodes to solve the CRC lymph node classification task. The multi-instance learning (MIL) framework is adopted in our method to handle the whole slide images (WSIs) of gigapixels in size at once and get rid of the labor-intensive and time-consuming detailed annotations. First, a transformer-based MIL model, DT-DSMIL, is proposed in this paper based on the deformable transformer backbone and the dual-stream MIL (DSMIL) framework. The local-level image features are extracted and aggregated with the deformable transformer, and the global-level image features are obtained with the DSMIL aggregator. The final classification decision is made based on both the local and the global-level features. After the effectiveness of our proposed DT-DSMIL model is demonstrated by comparing its performance with its predecessors, a diagnostic system is developed to detect, crop, and finally identify the single lymph nodes within the slides based on the DT-DSMIL and the Faster R-CNN model. The developed diagnostic model is trained and tested on a clinically collected CRC lymph node metastasis dataset composed of 843 slides (864 metastasis lymph nodes and 1415 non-metastatic lymph nodes), achieving the accuracy of 95.3% and the area under the receiver operating characteristic curve (AUC) of 0.9762 (95% confidence interval [CI]: 0.9607–0.9891) for the single lymph node classification. As for the lymph nodes with micro-metastasis and macro-metastasis, our diagnostic system achieves the AUC of 0.9816 (95% CI: 0.9659–0.9935) and 0.9902 (95% CI: 0.9787–0.9983), respectively. Moreover, the system shows reliable diagnostic region localizing performance: the model can always identify the most likely metastases, no matter the model’s predictions or manual labels, showing great potential in avoiding false negatives and discovering incorrectly labeled slides in actual clinical use.Graphical Abstract