Intramuscular lipomas are uncommon benign mesenchymal tumors which infiltrate skeletal muscle and are exceedingly rare in the head and neck region. Because of the infiltrating nature of the lesion and a high propensity for recurrence, they are sometimes difficult to distinguish from well-differentiated liposarcomas (WDLS). We report, the first case of an infiltrating lipoma of the temporal muscle in a 62-year-old white man who presented with a slow growing mass in the left temporal region. The histopathological examination showed diffuse infiltration of the striated muscle fibers by mature adipocytes. There were no lipoblasts or cells with atypical nuclei as described in WDLS. We performed interphase fluorescence in situ hybridization (FISH) analyses using painting probes for chromosome 12 and a specific probe for the MDM2 gene and comparative genomic hybridization. The results did not identify MDM2 or 12q amplification and therefore confirmed the benign nature of the lesion.