Background: Risk of contralateral nodal metastases in oropharyngeal squamous cell carcinoma (OPSCC) is currently based on clinical risk factors. We propose lymphatic mapping with single photon emission computed tomography (SPECT-CT) for tumor-specific delineation of lymphatic drainage to guide treatment. Methods: Retrospective review of lymphatic drainage patterns in cT1-2 OPSCC and contralateral cN0 neck with a nonoperative, awake injection of 99 m-Tc sulfur colloid and SPECT-CT. Results: Ten patients were reviewed. Primary sites included tonsil (n = 8, 80%) and tongue base (n = 2, 20%). All patients tolerated awake injections with no complications. Nine patients (90%) demonstrated satisfactory migration of radiotracer to neck node(s) with seven (78%) to the ipsilateral lateral neck, one (11%) to the ipsilateral lateral neck and retropharynx, and one (11%) to bilateral lateral neck nodes. Conclusions: Characterization of lymphatic drainage in OPSCC is feasible using a nonoperative injection technique and SPECT-CT. Drainage to the contralateral neck is rare, warranting further study to tailor treatment appropriately.