Clinicians described a metastatic breast cancer case in which palbociclib treatment preceded a rare chronic immune-mediated polyradiculoneuropathy with anti-neurofascin antibodies, mimicking CIDP. The report underscores how immune-targeted adverse events can present with overlapping phenotypes, complicating diagnosis and treatment decisions for patients on CDK4/6 inhibitors. For practice, the key takeaway is heightened awareness and early neurology evaluation when new neuropathy symptoms emerge during therapy, as well as careful immune workup to distinguish autoimmune syndromes from treatment-related or paraneoplastic causes.