Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), together encompassed in the term non-melanoma skin cancers (NMSC), are the most common cancers among fair-skinned populations. Individuating accurate risk stratification of NMSC patients is crucial to select different options among various treatment strategies. The majority of low risk NMSCs are easily treated with surgery, offering excellent cure rates and cosmetic results. Other treatment modalities include physical destruction (curettage, cautery and cryotherapy), chemical destruction (photodynamic therapy and topical 5-flurouracil) and immunomodulatory therapy (topical imiquimod). However, there is a subset of "high-risk" NMSC characterized by prognostic factors associated to aggressive behavior, such as tumor location and size, clinical margins, histopathological variants, recurrence or previous treatment. These lesions need to be treated accordingly also by mean of adjuvant treatments. The contribution of a multidisciplinary team is necessary to appropriately manage patients affected by advanced NMSC. The aim of these practical indications is to provide a useful guidance for risk stratification of NMSC patients in clinical setting and for consequential treatment choice, resulting in individualized management strategies.