Background: A significant portion of cutaneous melanoma may remain after subtotal incisional biopsy. The accuracy of microstaging and impact on clinical practice in this scenario are unknown. Objective: Our purpose was to examine microstaging accuracy of an initial incisional biopsy with a significant portion of the clinical lesion remaining (≥50%). Methods: Patients with cutaneous melanoma, diagnosed by incisional biopsy with ≥50% of the lesion remaining, were prospectively evaluated for microstaging accuracy, comparing initial Breslow depth (BD1) to final depth (BD2) after excision of the residual lesion. Impact on prognosis and treatment was also evaluated. Results: Two hundred fifty of 1783 patients (14%) presented with ≥50% residual clinical lesion after incisional biopsy. The mean BD1 was 0.66 mm; the mean BD2, 1.07 mm (P =. 001). After complete excision of the residual lesion, upstaging occurred in 21% and 10% became candidates for sentinel node biopsy. Conclusion: An incisional biopsy with ≥50% clinical lesion remaining afterward may be inadequate for accurate microstaging of melanoma. This scenario is relatively uncommon but clinically significant. © 2005 by the American Academy of Dermatology, Inc.