During a screening program, a 24-year-old woman presented an itchy nodule above the upper lip, 5 × 5 mm in size with irregular pigmentation, which had enlarged over the previous three weeks. Personal clinical history revealed a recurrent Herpes virus infection. Dermoscopy showed light brown irregular pigmentation, milia-like cysts and an atypical vascular pattern. Reflectance confocal microscopy revealed architectural, cytologic and vascular features suggestive of melanoma. A Tzanck test revealed multinucleated keratinocytes with the typical nuclei infected by Herpes virus. Our case shows that dermoscopy alone, despite its sensitivity and specificity, may not provide adequate diagnostic accuracy on which to base a surgical decision. Epiluminescence criteria should be considered together with a clinical evaluation of the lesion and the patient's clinical history. Reflectance-mode confocal microscopy confirmed the difficulty of presurgical diagnosis in this case, which highlights the importance of traditional cytological analysis in order to avoid unnecessary surgical treatment.