Several trials show a relationship between skin toxicity, response rate, and overall survival in cetuximab-treated patients. We analyzed our database to evaluate the importance of skin rash as a surrogate marker of favorable outcome in cancer patients referred to our institution in the last three years. We retrospectively analyzed 90 cetuximab-treated patients: 57 colon cancer patients, 10 NSCLC patients, 14 locally advanced esophageal cancer patients, and 9 miscellaneous. A significant correlation was observed between skin rash and response to therapy. Skin rash was experienced by 93% of PR and 100% of CR patients. The mean TTP was 184 days in patients showing skin rash and 94 days in patients without skin rash, respectively. On multivariate analysis, skin rash was demonstrated to be the only independent prognostic variable with regard to TTP. Patients who did not develop skin rash had a 2-fold greater likelihood to manifest tumor progression significantly earlier than patients who developed skin rash. In our series, a statistically significant correlation between rash, response rate, and TTP was demonstrated in 90 cetuximab-treated patients. Skin toxicity was confirmed as the only clinical variable able to predict the response to cetuximab.