Epiluminescence microscopy (ELM) strongly improves the separation of different types of cutaneous pigmented lesions (CPL) and facilitates the early diagnosis of cutaneous melanoma (CM). ELM alone is not 100% accurate in routine diagnosis, and should not be considered the only criterion in the diagnosis of high-risk skin lesions. We have however, demonstrated close agreement between ELM classification criteria and histology in 2,731 cutaneous lesions. In the past five years, our Melanoma Cooperative Group has evaluated 61,000 skin lesions from 30,000 individuals and identified 478 cutaneous melanomas. Most newly diagnosed patients had very early stage melanoma [299 (62%) were Stage I (203 Stage IA and 96 Stage IB), by the American Joint Committee on Cancer (AJCC) criteria]. We have compared data from the patient histories and clinical evaluations with ELM-based morphological patterns to better characterize skin lesions and minimize interpretative problems. From these comparisons, we propose new guidelines for the management of CPL to provide a standard diagnostic and therapeutic approaches and to foster the early identification of lesions at risk for malignant transformation.