Background Presenting signs/symptoms of skin cancer may aid in earlier detection and diagnosis. Objective We sought to compare prospectively collected, presenting signs/symptoms of malignant melanoma (MM), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and seborrheic keratosis (SK). Methods This analysis was part of a larger study on teledermatology involving 3039 skin neoplasms in 2152 patients at a Department of Veterans Affairs medical center. At presentation, participants were asked about signs/symptoms of specific skin lesions. In all, 912 biopsy-proven MM (39), BCC (411), SCC (238), and SK (224) were included in this analysis. Pearson χ 2 analyses were used to test associations of lesion type and specific signs/symptoms in pairwise comparisons. Results “No symptoms” was reported more often with MM (82%) as compared with BCC (relative risk [RR] 2.26, confidence interval [CI] 1.86, 2.75), SCC (RR 3.31, CI 2.54, 4.32), or SK (RR 2.0, CI 1.61, 2.48; all P < .0001). Tenderness was more commonly reported with SCC (40%) as compared with MM (RR 15.9, CI 2.28, 110.69), SK (RR 3.0, CI 2.11, 4.39), or BCC (RR 2.6, CI 1.97, 3.38; all P < .0001). Bleeding was more commonly reported with BCC (37%) as compared with SK (RR 2.3, CI 1.67, 3.20), SCC (RR 1.6, CI 1.22, 2.05), or MM (RR 29.8, CI 1.89, 469.65; all P ≤ .007). Limitations The small number of MM and study population characteristics (elderly, Caucasian, male) limit generalizability. Conclusion This study describes common signs/symptoms of BCC, SCC, and SK. Our findings suggest that MM may be asymptomatic more often than previously recognized.