Abstract:Background and Aims Hepatocellular carcinoma (HCC) presenting initially with bone metastasis is uncommon, and metastasis to the appendicular skeleton is particularly rare. These cases often lack typical liver disease history, elevated alpha-fetoprotein (AFP), or characteristic imaging findings, leading to frequent misdiagnosis or delayed diagnosis. This study reports a rare case of occult HCC presenting with humeral metastasis and reviews the literature to improve clinical recognition and management.Methods The clinical data of a 42-year-old male patient presenting with humeral metastasis as the initial manifestation admitted in August 2025 were retrospectively analyzed, including laboratory tests, multimodal imaging findings, histopathological and immunohistochemical results, treatment, and follow-up outcomes. Relevant literature was also reviewed.Results The patient presented with left shoulder pain. Imaging revealed osteolytic destruction of the left humerus. PET/CT incidentally detected multiple hepatic lesions without significant FDG uptake. Contrast-enhanced ultrasound demonstrated atypical enhancement patterns, initially suggesting a perivascular epithelioid cell tumor. Histopathological and immunohistochemical examination of biopsy specimens from both the humeral and hepatic lesions confirmed moderately differentiated hepatocellular carcinoma with humeral metastasis (CNLC stage IIIb). The patient received systemic therapy with sintilimab plus bevacizumab, followed by transcatheter arterial chemoembolization. After 6 months of follow-up, the intrahepatic lesions had decreased in size, the bone metastasis remained stable, and pain symptoms were significantly relieved.Conclusion HCC presenting with humeral metastasis as the initial manifestation is extremely rare and may lack typical imaging and serological features. Clinicians should consider HCC in patients with unexplained bone metastasis even in the absence of liver disease history or elevated AFP. Multimodal imaging and pathological biopsy are essential for accurate diagnosis and appropriate management.