To determine if the sonographic appearance of cavernous hemangiomas of the liver correlated with their detectability on Tc-99m labeled red blood cell (RBC) SPECT scintigraphy, studies of 30 cavernous hemangiomas, 14 with typical and 16 with atypical sonographic appearance, were retrospectively reviewed. The 14 typical hemangiomas had uniform hyperechoic sonographic appearance, and ranged in size from 0.8-3.9 cm (mean 2.0 cm). The 16 atypical hemangiomas ranged in size from 1.0-9.0 cm (mean 3.4 cm) and sonographic appearance was hypoechoic (n = 9), echogenic (with hypoechoic or cystic center [n = 3] or with irregular margins or shape [n = 2]); or heterogeneous (n = 2). Nine of 14 (64%) typical cavernous hemangiomas were identified on SPECT, compared with 15 of 16 (94%) atypical cavernous hemangiomas (P = 0.07). All 18 lesions ≥2 cm (6 typical, 12 atypical) were identified on SPECT. Sensitivity of SPECT for hemangiomas of smaller than 2 cm was 38% (3 of 8) for those with typical and 75% (3 of 4) for those with atypical sonographic appearance. Four of the five typical hemangiomas not seen on SPECT were ≤1 cm in at least one dimension. Detection of cavernous hemangiomas on RBC liver SPECT is primarily dependent on lesion size, with the influence of the sonographic appearance of these lesions mostly associated with the smaller size of those with typical characteristics.