Malignant melanoma has been thought to evolve from junctional proliferation of atypical melanocytes, through a stage characterized by large junctional nests, into an invasive an ultimately metastasizing neoplasm. Sequential histologic study of a case of lentigo maligna melanoma suggested that the tumor progressed by development of more aggressive lesions in adjacent skin, rather than by evolution of preexisting lower-grade lesions. The higher grade of the later-developing lesions may result from greater exposure to carcinogens, perhaps by virtue of greater solar exposure prior to onset. Neural factors may be responsible for the progressive development of multi-centric lesions within a restricted region of skin (field effect). We recommend investigation of neurogenic influences in human melanoma, particularly with regard to the role of nerve growth factor.