Oncological treatment is currently directed toward a tailored therapy concept.Squamous cell carcinoma of the anal canal could be considered a suitable platform to test new therapeutic strategies to minimize treatment morbidity.Standard of care for patients with anal canal cancer consists of a combination of radiotherapy and chemotherapy.This treatment has led to a high rate of local control and a 60% cure rate with preservation of the anal sphincter,thus replacing surgical abdominoperineal resection.Lymph node metastases represent a critical independent prognostic factor for local recurrence and survival.Mesorectal and iliac lymph nodes are usually included in the radiation field,whereas the inclusion of inguinal regions still remains controversial because of the subsequent adverse side effects.Sentinel lymph node biopsies could clearly identify inguinal node-positive patients eligible for therapeutic groin irradiation.A sentinel lymph node navigation procedure is reported here to be a feasible and effective method for establishing the true inguinal node status in patients suffering from anal canal cancer.Based on the results of sentinel node biopsies,a selective approach could be proposed where node-positive patients could be selected for inguinal node irradiation while node-negative patients could take advantage of inguinal sparing irradiation,thus avoiding toxic side effects. Oncological treatment is currently directed toward a tailored therapy concept.Squamous cell carcinoma of the anal canal could be considered a suitable platform to test new therapeutic strategies to minimize treatment morbidity.Standard of care for patients with anal canal cancer consists of a combination of radiotherapy and chemotherapy.This treatment has led to a high rate of local control and a 60% cure rate with preservation of the anal sphincter,thus substituted surgical abdominoperineal resection.Lymph node metastases represent a critical independent prognostic factor for local recurrence and survival.Mesorectal and iliac Lymph nodes are usually included in the radiation field, whereas the inclusion of inguinal regions still remains controversial because of the following adverse side effects.Sentinel lymph node biopsies could clearly identify inguinal node-positive patients eligible for therapeutic groin irradiation.A sentinel lymph node navigation Procedure is reported here to be a Feasible and effective method for establishing the true inguinal node status in patients suffering from anal canal cancer.Based on the results of sentinel node biopsies, a selective approach could be proposed where node-positive patients could be selected for inguinal node irradiation while node-negative Patients could take advantage of inguinal sparing irradiation,thus avoiding toxic side effects.