An adult male Rio Fuerte beaded lizard (Heloderma horridum exasperatum) was examined because of a history of anorexia and lethargy of one week duration. Diagnostic tests included a physical exam, complete blood cell count, plasma biochemistries, whole-body radiographs, and ultrasonography. The physical exam revealed the presence of a large mass in the midcoelomic cavity. Radiographs confirmed the presence of the midcoelomic mass and showed a smaller mass in the right cranial lung field. The ultrasonogram showed a homogeneous mass with soft tissue echogenicity. A fine-needle aspirate was collected, and the cytology results were suggestive of a melanophoroma. Exploratory surgery revealed a large mass (10 × 6 cm) within the right lung, with extensive adhesions to the caudolateral margin of the right liver lobe. The smaller mass (2 × 3 cm) was within the cranial aspect of the right lung. A right pulmonectomy and partial hepatectomy were performed to remove the tumors. The animal died 3.5-yr postsurgery, and histopathologic evaluation did not show evidence of melanophoroma in any of the tissues evaluated.