Spindle cell lipoma (SCL) is an uncommon soft tissue neoplasm that may provide diagnostic difficulty to the histopathologist. Four retrospectively identified SCLs were evaluated immunohistochemically with a broad panel of antibodies (CD34, factor XIIIa, S-100, actin and factor VIII). All four SCLs were strongly CD34 positive (95 to 100% of cells) and focally factor XIIIa positive (average 16% of cells). Tumor cells were S-100, actin and factor VIII negative. Dermatofibrosarcoma protuberans, neurofibroma, schwannoma and angiolipoma are CD34 positive tumors that have some similar histologic features to SCL and may be considered in the differential diagnosis. Differentiation is possible using a broad panel of immunostains and routine diagnostic criteria.