Oropharyngeal squamous cell carcinoma is a prevalent neoplastic condition. The incidence rate in Malaysia is rising, with human papillomavirus (HPV) infection being recognized as a significant contributing factor. Hence, it is paramount for physicians to effectively diagnose and identify significant indicators that may indicate a malignant etiology. In this study, we present a case of a middle-aged Malay male who presented with the primary symptom of persistent right throat discomfort for one month. The preliminary presentation, blood parameters, and initial histopathological examination (HPE) findings indicate the presence of an infection. However, despite undergoing several medical treatments, the patient's symptoms remain, albeit with only minor clinical improvement. Subsequently, the patient underwent a biopsy under general anesthesia, which subsequently yielded a report indicating the presence of oropharyngeal squamous cell carcinoma with a negative p16 status. Therefore, it is imperative for clinicians to possess knowledge of warning flags and exercise vigilance when encountering a patient who fails to respond despite thorough and precise evaluation. If there is a strong suspicion of malignancy, it is imperative to do a comprehensive clinical investigation and regular monitoring.