Neurofollicular hamartoma is a recently described lesion with a distinct pilosebaceous and spindle cell proliferation. Neurofollicular hamartoma is composed of spindle cells haphazardly arranged in a fibromyxoid stroma closely associated with an abnormal hyperplasia of folliculosebaceous units. Although this histologic pattern has been classified as "neurofollicular," all cases reported thus far have had only scattered spindle cells with S-100 positivity. We present a case of neurofollicular hamartoma with strong and diffusely positive staining of spindled cells for S-100 protein. This lesion also shows scattered positivity of spindle cells for monoclonal neuron specific enolase and synaptophysin. We interpret the results of immunostains of this lesion as evidence for neural differentiation. This case validates the concept of "neurofollicular" hamartoma.