BACKGROUND: For squamous-cell carcinoma of the anal canal, most delineation guidelines recommend elective irradiation of the external iliac lymph nodes (LNS) and the upper pelvic LNS (located above the inferior aspect of the sacroiliac joints), regardless of clinical stage. However, neither of these regions is the first-echelon nodal station for anal primaries, and there is no conclusive evidence on the risk of microscopic involvement of these LNS in patients with cT1-2N0 disease. The recommendation to include these regions in the elective CTV for early anal canal cancer is based on historical practice, reflecting lymph node regions in earlier AP-PA fields, rather than conclusive evidence. PATIENTS AND METHODS: A systematic review of the literature and a meta-analysis were performed to determine the rates of regional recurrence in the upper pelvic and external iliac LNS in patients with early anal canal cancer (cT1-2N0) treated with radio(chemo)therapy without elective nodal irradiation (ENI) of these LNS. RESULTS: One prospective and eight retrospective studies were included in the meta-analysis. The pooled weighted rate of regional recurrence in the upper pelvic LNS was 0.9 % (95 % confidence interval [CI]: 0.1-1.8 %) among 495 cT1-2N0 patients treated with ENI not covering these LNS. None of 233 patients treated with ENI not covering external iliac LNS had a recurrence in this region after radio(chemo)therapy. CONCLUSION: Low risk of regional recurrence in the untreated upper pelvic and external iliac LNS suggests they can be confidently excluded from the elective nodal CTV for patients with early squamous cell anal canal cancer.