Positron Emission Tomography (PET) using the glucose analog 2-deoxy-2-[18F]fluoro-d-glucose (18FDG) is a common imaging modality for diagnosis and management of many human malignancies. We evaluated 18FDG-PET in dogs with either multicentric lymphoma (LSA) or cutaneous mast cell tumor (MCT). A prototype large field-of-view PET scanner was used to collect whole-body images in nine dogs with LSA or MCT. Both tumors were characterized by avidity for 18FDG. In dogs with LSA, 18FDG-PET correctly identified involvement of superficial and internal lymph nodes, liver, and spleen. Repeated PET scans after induction chemotherapy demonstrated resolution of abnormal 18FDG uptake within these sites. In dogs with MCT, 18FDG-PET correctly identified MCT metastasis to regional lymph nodes in all dogs in which this was suspected or confirmed with cytology or biopsy before the PET scan. In two dogs, additional sites of mast cell disease were identified with 18FDG-PET that were undetected on physical examination and/or regional lymph node cytology. 18FDG-PET holds promise as a whole-body staging method for canine LSA and MCT.