Cranial nerve thickening as an initial isolated presentation of CNS lymphoma is rare. Once an extremely rare neoplasm, primary lymphoma of the central nervous system (CNS) now ranks only next to meningiomas and low-grade astrocytomas in prevalence. Multiple cranial nerve thickening can be a feature of primary CNS lymphoma. Here we report a case of a 45-year-old immunocompetent female who presented with relapsing remitting multiple cranial nerve thickening as an initial feature of primary CNS lymphoma without any other brain or spinal cord lesions.