The occurrence of primary cutaneous ganglioneuroma is rare. We report 2 separate cases of primary cutaneous ganglioneuroma, both of which are associated with prominent overlying hyperkeratosis. The first case was in a 38-year-old woman with overlying verrucous keratosis. The second case was in a 93-year-old man with epidermal changes reminiscent of a seborrheic keratosis. Histologically, both lesions were composed of a proliferation of hyperplastic nerve fibers with spindled Schwann cells and axons with intermingled ganglion cells. Immunohistochemistry for neurofilament highlighted nerve fascicles; S100 protein displayed the associated Schwann cells, and neuron-specific enolase stained the interspersed ganglion cells. Variation in immunohistochemical staining was present between the 2 cases. A review of the literature demonstrates variable immunohistochemical staining of ganglion and Schwann cells in prior cases. Familiarity with these findings is important in establishing a diagnosis. The significance of the associated hyperkeratosis remains speculative.