A 65-year-old female suffering from epigastric discomfort and weight loss was admitted to our hospital. She had a history of hepatolithiasis. Laboratory tests revealed that serum levels of carbohydrate antigen 72-4 (CA72-4), CA19-9, and carcinoembryonic antigen were significantly increased. Gastroscopy was indicated and a large ulcer at the gastric angle was identified (Fig. 1A). Pathological examination of the biopsy tissue confirmed the diagnosis of signet ring cell carcinoma (Fig. 1B). A subsequent abdominal computed tomography (CT) revealed a large liver mass and multiple enlarged regional lymph nodes, making advanced gastric cancer our primary concern. 18F-fluorodeoxyglucose positron emission tomography/CT (¹⁸F-FDG PET/CT) was performed for further staging. An intense FDG-avid liver mass, multiple hypermetabolic lymph nodes and bone lesions were identified (Fig. 2A–C). Intriguingly, there was only faint FDG uptake at the signet ring cell carcinoma of the stomach (Fig. 2D and 2E). In turn, we performed an ultrasonography-guided needle biopsy of the liver mass. Histopathologic examination and immunohistochemical staining validated the diagnosis of hepatic squamous cell carcinoma (Fig. 2F–H). Considering FDG PET/CT and ear, nose, and throat (ENT) examination were negative at the common primary sites of squamous cell carcinoma (nasopharynx, neck, lung, cervix, and skin) and the distribution patter of the metastatic lymph nodes, the diagnosis of advanced primary hepatic squamous cell carcinoma was established.