The Great Imitator strikes again: a hepatobiliary puzzle unraveled by a skin biopsy.

Hepatic syphilis is a rare and often overlooked cause of cholestatic liver injury. A 65-year-old male presented with new-onset cholestasis, severe pruritus, weight loss, and marked elevation of CA 19-9. MRCP revealed irregular ductal calibers in a PSC-like pattern with biliary dilatation predominantly on the right side with stricture of the central bile ducts with a central filling defect, initially raising concern for occult cholangiocarcinoma. Histology from cholangioscopic bile duct biopsies demonstrated nonspecific inflammation. Concurrent dermatologic evaluation of a persistent rash led to a punch biopsy showing plasma-cell-rich inflammation, prompting serologic testing that confirmed active syphilis. Spirochetes were visualized on bile duct tissue using specific staining. This case highlights the protean manifestations of Treponema pallidum, including its ability to mimic PSC and even malignancy. Clinicians should maintain a low threshold for syphilis testing in unexplained cholestasis, even in the absence of overt risk factors, to avoid misdiagnosis and delayed treatment.