Actinic keratosis is considered a precancerous lesion, constituting a precursor to squamous cell carcinoma (SCC) formation. Perineural invasion has been observed in patients with cutaneous carcinoma due to local subcutaneous tissue destruction and primarily involves the trigeminal nerve due to rich innervation provided by the supraorbital nerve in addition to the facial nerve. An unusual case of perineural infiltration and orbital invasion of squamous cell carcinoma associated with actinic keratosis is presented. A 70-year-old Caucasian woman presented with complete left eye ophthalmoplegia, total left upper-eyelid ptosis, and facial pain with paresthesia. Computed tomography revealed a process of the soft tissues in the left cheek infiltrating the infraorbital canal, pterygopalatine fossa, inferior orbital fissure, and left cavernous sinus with periosteal adherence. Magnetic resonance imaging revealed pathological extension via the left infraorbital canal with a considerable area of necrosis. Treatment of facial actinic keratosis may not prevent malignant transformation and can delay diagnosis and treatment of SCC. A deep biopsy appears to be essential for a correct diagnosis. Perineural spread of cutaneous SCC may be characterized by insidious progression in the cranial trigeminal nerve, abnormal ocular motility, diplopia, or external ophthalmoplegia.