An 80-year-old female with a history of idiopathic thrombocytopenic purpura and splenectomy presented to our institution with seven days of fevers at night, chills, night sweats, and weight loss. She lived with her husband and was independent in her activities of daily living. She was asymptomatic one week prior to initial presentation to the emergency room. Upon admission, she appeared fatigued with an exam remarkable for icterus, enlarged right neck and left supraclavicular lymph nodes (LNs), hepatomegaly, and right upper quadrant tenderness. Laboratory tests revealed a WBC of 19.7 x 109/L with a differential of 31% neutrophils, 58% lymphocytes, and 11% monocytes. Liver function tests (LFTs) revealed an alkaline phosphatase of 595 mu/L, aspartate aminotransferase of 281 mu/L, alanine aminotransferase of 200 mu/L, and a total bilirubin of 2 mg/dL. Abdominal ultrasound noted multiple enlarged porta hepatis LNs and findings suggestive of choledocholithiasis. MRCP revealed no choledocholithiasis or ductal dilatation but revealed significant interaortocaval, periportal, and common hepatic enlarged LNs. A CT scan of the chest revealed enlarged bilateral axillary and significant anterior and superior mediastinal LNs suggestive of lymphoma. An infectious disease workup was negative for viral hepatitis, mononucleosis (monospot test), coccidiomycosis, ehrlichiosis, rickettsia, QuantiFERON-TB Gold In-Tube, histoplasmosis, blastomycosis, CMV, and toxoplasmosis, and blood cultures were also negative. An excisional biopsy of a right neck LN revealed an atypical lymphoid proliferation. The surgical team initially recommended a mediastinoscopy with mediastinal LN sampling for a more adequate specimen, but a multidisciplinary group meeting concluded that ultrasound-guided needle percutaneous liver parenchyma and periportal LNs biopsies should be performed due to lower invasiveness and higher diagnostic yield potential. Liver and retroperitoneal LN core biopsies revealed an atypical lymphoid infiltrate (Figures 1(a) and 2(a)). EBV anti-EBNA and anti-VCA IgG/IgM were nonreactive; however, serum EBV DNA by PCR was elevated (146,500 copies/mL), suggesting acute systemic EBV infection. Furthermore, in situ hybridization analysis of the liver and LN tissue specimens was diffusely positive for EBV-encoded RNA (Figures 1(b) and 2(b)), further confirming EBV as the cause of her constellation of symptoms in our seronegative patient. Immunoperoxidase stains of tissue specimen revealed an atypical lymphoid infiltrate composed of a mixed population of both B- and T-cells. A Ki-67 stain indicated that the infiltrate appeared proliferative. Flow cytometric immunophenotyping identified lymphocytes comprising 78% of total cells and consisted of a mixture of phenotypically unremarkable T-cells (66%), polytypic B-cells (32%), and NK cells (2%). There did not appear to be atypical expression of CD4 and CD8 stains. The histologic and flow cytometric immunophenotyping were not diagnostic of a B-cell, T-cell, or Hodgkin's lymphoma. The patient was started on ganciclovir and subsequently switched to valganciclovir for 3 weeks on discharge. At the time of discharge (after a week of hospitalization) and during followup, the patient was asymptomatic and showed improvement in her liver function test (LFT).