BACKGROUND Paraneoplastic syndromes remain poorly understood and manifest as multifaceted clinical symptoms, making their diagnosis difficult. Cholestasis can be observed in various malignancies. In rare cases, it can be a paraneoplastic manifestation, most often associated with renal cell carcinoma and other urogenital tumors, as well as with bronchial carcinoma. The classical form of Stauffer syndrome presents with a reversible anicteric increase of cholestatic liver function tests, thrombocytosis, coagulation impairment, and hepatosplenomegaly, without any proven hepatobiliary obstruction or metastases. CASE SUMMARY We report a patient who presented with elevated liver enzymes, cholestatic jaundice, weight loss and pruritus, in whom renal cell carcinoma was incidentally found during hospitalization. Clinical, laboratory, and imaging tests excluded primary hepatic cause or metastatic disease. Jaundice and laboratory abnormalities reversed completely a few months after nephrectomy. This case is an example of the many sides of renal cell carcinoma, and it focuses the clinicians’ attention on the differential diagnosis of cholestasis, including Stauffer syndrome and its variant. Thus, the correct diagnosis can be straightforward and the associated malignancy can be treated promptly. All cases should be followed up with a multidisciplinary team. Interleukin (IL)-6 is proposed to contribute to the pathophysiology of the condition. The probable mechanism is proinflammatory activity by the IL-6 cytokine, causing elevation of C-reactive protein and haptoglobin and inhibition of hepatobiliary transporter gene expression, impairing biliary outflow. CONCLUSION Despite being rare, Stauffer syndrome is a potentially reversible paraneoplastic condition, when the primary cause is treatable. This syndrome should be considered by clinicians because of the remediable liver disturbance, after successful treatment of the underlying malignancy.