A 74-year-old woman who presented initially with trigeminal neuralgia of the left forehead and scalp was later found to have a poorly differentiated squamous cell carcinoma (SCC) with large-nerve perineural and intraneural invasion of the left supraorbital nerve. Negative histopathologic margins were achieved in three stages of permanent fixed tissue en face processing and the final defect was repaired with a large rotation flap. Approximately one month after repair, the patient presented with new-onset diplopia and was found to have a complete left cranial nerve VI palsy suspicious for continued disease spread. MRI confirmed perineural spread along the ophthalmic branch of the trigeminal nerve through the superior orbital fissure into the cavernous sinus. She was subsequently treated with radiation therapy (66Gy in 33 fractions). The involvement of two distinct cranial nerves by perineural invasion is uncommon and has mostly been described involving branches of the trigeminal and facial nerves. This case highlights the rare presentation of perineural invasion involving both the trigeminal nerve and the abducens nerve. Anatomically, this clinical presentation can be explained by the retrograde perineural spread along the ophthalmic branch of the trigeminal nerve through the supraorbital fossa into the cavernous sinus where these two nerves are in close proximity.