Objectives: Staging of the cN0 neck with sentinel node biopsy (SNB) in early-stage oral squamous cell carcinoma (OSCC) is validated in patients with a previously untreated neck. We aimed to investigate the feasibility and diagnostic accuracy of SNB and unexpected drainage patterns in patients with cT1-T2N0 OSCC and a history of previous head and neck cancer comprising treatment of the neck, that is, surgery, radiotherapy, or both. Methods: Fifty patients with a previously treated neck diagnosed with a new primary or recurrent cN0 OSCC between 2014 and 2021 were included and retrospectively analyzed. Feasibility was assessed by the rate of successfully performed SNB neck staging procedures. Based on follow-up data, the diagnostic performance of SNB was evaluated by calculation of negative predictive value (NPV) and false omission rate (FOR). Results: A SNB staging procedure was successfully performed in 76% (38/50) of the patients. Technical failures were due to the lack of drainage preoperatively or failure in intraoperative SN detection. In patients successfully staged with SNB, the rate of a positive SN was 13% (5/38). In the SNB-negative group, no patients were diagnosed with a regional node recurrence during follow-up, and the NPV and FOR were 100% and 0%, respectively. Unexpected lymphatic drainage occurred in 32% (12/38) of the patients. Conclusion: SNB is technically feasible in cT1-2N0 OSCC patients with a previously treated neck with a high diagnostic accuracy. Importantly, SNB enables the detection of individual and unexpected lymphatic drainage patterns.