Background: Diffuse nodular nevus of the iris is an uncommon condition that presents with multiple verrucous excrescences distributed diffusely on the iris surface. Methods: The authors describe 30 patients with bilateral diffuse iris nodular nevi and report associations with bilateral congenital cataract, neurofibromatosis, oculodermal melanocytosis, congenital ptosis, morning glory anomaly, Axenfeld anomaly, or Peters anomaly. Results: Iris nodules were uniform in size and distribution and were brown, as was the surrounding iris. Light and electron microscopy of iridectomy specimens from one patient showed elevated plaques composed of aggregates of plump, lightly pigmented nevoid cells interwoven with mature, densely pigmented spindle-shaped uveal melanocytes. Conclusions: The authors report the largest clinical series and first ultrastructural description of bilateral diffuse iris nodular nevi, vuhich represents a variant of neural crest development. No ocular complications could be attributed to the iris nodules, which should be differentiated from Lisch nodules and other pathologic iris lesions.