The gallbladder is involved by a wide variety of non-epithelial tumors, apart from mesenchymal neoplasms. Visceral malignant melanoma develops in the biliary tract, including the gallbladder. As both primary and metastatic gallbladder melanomas may show similar of the same growth patterns, the differential diagnosis between these two conditions is often difficult. Primary gallbladder melanoma is more likely if the tumor shows a polypoid or lobulated and in particular papillary growth pattern, is a solitary lesion, and is associated with junctional activity in the adjacent mucosa. In contrast, metastatic lesions are more commonly multiple, flat, and without junctional changes. Apart from neuroendocrine tumors, other neuroectodermal neoplasms can develop as primary tumors in the gallbladder. Rare primary neoplasms in this organ include germ cell tumors, rhabdoid tumors, perivascular epithelioid cell tumors, and hemolymphatic neoplasms. Apart from malignant melanoma, numerous other malignancies can metastasize to the gallbladder, renal cell carcinoma being a particularly common metastasizing tumor. Malignant Melanoma of the Gallbladder Pathogenic Pathways Few melanocytes are present in the normal gallbladder mucosa, and it has been suggested that malignant melanomas take their origin from these cells that have spread from the neural crest to the gallbladder during oncogenesis. Primitive Neuroectodermal Tumor (PNET) of the Gallbladder Differential Diagnosis Differential diagnosis on conventionally stained sections mainly includes other small cell tumors occurring in the gallbladder, e.g., small cell carcinoma or lymphoma. Differential Diagnosis Gallbladder paraganglioma may occur as a component of multiple paragangliomas, involving the common bile duct and the liver in addition to the gallbladder (Ferrell et al. 1990).