Indeterminate fibrohistiocytic lesions of the skin share histological and immunohistochemical features of both benign fibrous histiocytoma/dermatofibroma and dermatofibrosarcoma protuberans (DFSP). Unlike dermatofibroma, DFSP harbors recurrent genetic aberrations resulting in the fusion of COL1A1 on chromosome 17 and PDGFB on chromosome 22. Because indeterminate fibrohistiocytic lesions share some features with DFSP, they were evaluated for the possible presence of COL1A1-PDGFB chimeric transcripts. Twelve formalin-fixed paraffin-embedded cases were examined for COL1A1-PDGFB chimeric transcripts using a previously validated sensitive multiplex reverse transcriptase-polymerase chain reaction assay. The median patient age was 52.5 years (33-70 years) with 9 females and 3 males. The most common site was the extremities (n = 8) followed by the trunk (n = 2) and the head and neck region (n = 2). All demonstrated the expected reactivity for both CD34 and factor XIIIa, and the majority focally infiltrated into subcutaneous fat. Of the 6 patients with follow-up, 2 had residual tumor excised, but no patient developed a recurrence. None of the tumors harbored COL1A1-PDGFB fusion transcripts identified by reverse transcriptase-polymerase chain reaction. Although indeterminate fibrohistiocytic lesions share some features with DFSP, the lack of COL1A1-PDGFB chimeric transcripts suggests that they are distinct entities.