Neurofibromatosis type 1 (NF1) is a common autosomal dominant hamartomatous disorder, which is considered to be a neurocristopathy. Uveal melanoma, also of neural crest origin, is the most common primary malignant intraocular tumor in adults. The association of NF1 and uveal melanoma is controversial. We present a clinicopathologic report of iris melanoma in a patient with NF1 and review the literature for a possible causal association. To our knowledge, only 18 cases of uveal melanoma, including three cases of iris melanoma, have been reported in association with NF1. On the basis of the prevalence of NF1 (1 in 3000) and the prevalence of uveal melanoma (1 in 13,500), it can be estimated that approximately seven patients with NF1 in the United States would have an associated uveal melanoma by chance alone. We conclude that despite the theoretical possibility of a causal association of uveal melanoma and NF1, it may still be regarded as coincidental in the absence of any strong evidence to the contrary.