Chondroblastoma (CB) is a relatively rare yet well-studied benign neoplasm of bone. The purported neoplastic cell is the chondroblast, a cell which normally populates areas of secondary ossification. Numerous studies have shown that CB overwhelmingly arises from the epimetaphyseal region of skeletally immature individuals. Only rare cases have been reported in the diaphyseal region, and many of these involve metacarpals or metatarsals, which may lack a true anatomic diaphysis. The remaining cases of diaphyseal CBs synchronously involve the neighboring epimetaphysis, making determination of the initiation point impossible. We report a case of a CB isolated to the radiologic femoral diaphysis. To our knowledge, this is the first case of a diaphyseal-based CB to be reported in the pathology literature and only the second case published overall.