A 17-year-old male intact leopard gecko (Eublepharis macularius) was presented to a specialty referral hospital for lethargy, abdominal distension, exercise intolerance, and rapid weight loss. Physical exam revealed ascites and bilateral subcutaneous edema. A single dose trial of furosemide (1 mg/kg IM) was administered and the gecko responded positively, therefore, cardiac disease was suspected as the underlying cause. An echocardiogram was recommended but financial constraints initially precluded this option. Oral furosemide (1 mg/kg) was started, with dose frequency titrated to clinical response with frequent rechecks over a two-month period. Dose frequency ranged from q24h to q72h. The clinical signs were best controlled on 1 mg/kg PO q24h, though ultimately the ascites, anorexia, and lethargy continued to progress. Coelomic ultrasonography performed two months after initial presentation revealed a large (19 x 14 x 14 mm) focal irregularly marginated heterogeneous cavitated mass associated with the right side of the heart. There was also a large volume of echogenic pericardial effusion. Furthermore, subjective diffuse hepatomegaly and small volume anechoic coelomic effusion were appreciated. Primary cardiac neoplasia causing secondary hepatomegaly was suspected, and enalapril (1 mg/kg PO q24h) was started. After passing away one month later, necropsy confirmed the heart mass was a pericardial mesothelioma. Verhoff staining demonstrated evidence of elastin fiber disarray. Pancytokeratin stain of the mass was “strongly positive.” Vimentin stain was “fairly positive.” Cardiac neoplasia is rarely documented in reptiles but can be diagnosed and treated antemortem. Further research is indicated to determine optimal patient management.