The purpose of this study was to evaluate the use of combined transmission and emission tomography (TET) for correct localisation of heterotopic splenic tissue and differentiation of splenosis from other masses. The TET technique comprises the fusion of SPET and CT data obtained using the same imaging device to allow perfect overlap of anatomical and functional images. TET was performed in seven patients who either had haematological disorders and relapsing anaemia or thrombocytopenia after splenectomy or were under immunosuppression for different reasons. These patients presented 20 equivocal lesions on CT or MRI. Presence of splenic tissue was investigated using technetium-99m labelled colloids or heat-damaged red blood cells. Findings of spleen scintigraphy, TET and CT or MRI were compared with respect to localisation of splenosis and correct classification of lesions by CT or MRI. Histological validation was achieved by surgery or biopsy in all cases. All 20 lesions demonstrated by CT or MRI were correctly classified by TET as splenosis. Three additional lesions initially overlooked by CT or MRI could be detected. Diagnostic relevance was highest for intrahepatic, intrapulmonary or pleural splenic implants. It is concluded that TET allows exact localisation of heterotopic splenic tissue in patients with suspected splenosis.