Primary intraosseous squamous cell carcinoma (PIOSCC) is an uncommon malignant neoplasm arising within the jawbone, without initial connection to the oral mucosa. It is believed to originate from the malignant transformation of odontogenic epithelial remnants, cysts, or tumors. Involvement of the maxilla is exceedingly rare compared to the mandible. The clinical presentation and radiographic features of PIOSCC are often variable and non-specific, which may complicate early diagnosis and lead to confusion with other odontogenic or inflammatory lesions. This case report describes a rare occurrence of PIOSCC developing from an odontogenic keratocyst (OKC) in the maxilla of a 35-year-old female patient. The report discusses the possible mechanisms underlying malignant transformation within odontogenic cysts, emphasizes the biological behavior of this neoplasm, and delineates the characteristic clinical, radiological, and histopathological findings associated with this rare entity.