Abstract: We present a case that highlights the use of two maneuvers useful in the diagnosis of spindle cell melanoma. A shave biopsy from the cheek of a 58-year-old man demonstrated a thin invasive melanoma of 0.3 mm thickness with a less than 2-mm-wide intra-epidermal component. Below this melanocytic lesion, but not contiguous with it, there was a transected S-100-positive and Melan-A-negative spindle cell proliferation. Upon re-excision, no residuum of conventional melanoma was identified, but a residual spindle cell neoplasm that was 4 mm in diameter, nodular, well-circumscribed, cytologically bland, and S-100 positive was noted. At our consensus conference, our group favored neurofibroma but agreed that spindle cell melanoma could not be excluded based on histopathologic features alone. To further address the differential diagnosis, we performed CD34 staining that demonstrated lack of a CD34 fingerprint. We also completed array-based comparative genomic hybridization, which demonstrated gain of chromosome 6p, loss of 6p and gain of 7. These two methods of analysis support a diagnosis of spindle cell melanoma.