Background: Rational follow-up guidelines for skin cancer patients should be based on the risk of three separate events: cancer recurrence, cancer metastasis, and the development of subsequent skin cancers. However, currently no guidelines exist for follow-up of patients with squamous cell carcinoma of the skin (SCC), which take into account all three of these risks. Objective: The purpose of this study is to establish rational minimum guidelines for follow-up of patients with SCC. To do this, we first must determine the risk of SCC patients for the development of subsequent skin cancers. Combining these data with previously published data on SCC recurrence and SCC metastasis, we then propose guidelines for follow-up of patients with SCC. Methods: We followed up 101 SCC patients on a yearly basis for 5 years after treatment and recorded the date and site of subsequent nonmelanoma skin cancers (NMSCs). Results: Thirty percent of SCC patients developed additional SCCs and 52% developed subsequent NMSCs within 5 years of therapy for their first SCC. Patients showing the highest risk of subsequent NMSC were those presenting with multiple SCC, SCC greater than 1 cm in diameter, SCC requiring more than 1 Mohs surgery layer to remove, or SCC occurring on the scalp, ear, nose, or extremities. One hundred percent of subsequent NMSCs were detected by the fourth year of follow-up; 54% of these occurred within the first year of follow-up. Conclusion: After combining our data with previously published studies of SCC recurrence and metastasis, we recommend that all patients with SCC be followed up for at least 4 years after treatment. Moreover, because most subsequent NMSCs, SCC recurrences, and SCC metastases developed early in the follow-up period, we recommend that patients be reexamined at least every 3 months during the first year of follow-up and every 6 months thereafter. It must be stressed that these are meant as minimum follow-up guidelines.