The diagnosis of multiple sclerosis (MS) is primarily clinical and supported by paraclinical tests; however, a wide range of neurological and systemic diseases can mimic MS. Recognizing clinical red flags—features atypical for MS—is essential to avoid misdiagnosis. This chapter provides an overview of important clinical red flags encountered in MS differential diagnosis, organized by symptom domains. Red flags include bilateral or sequential optic neuritis, systemic symptoms such as fever, rash, or arthritis; early and severe cognitive impairment; epileptic seizures; dominating cerebellar ataxia; or involvement of the peripheral nervous system. Other warning signs are the presence of cardiovascular manifestations, cranial neuropathies, extrapyramidal syndromes, musculoskeletal complaints, and symptoms, such as hearing loss, headache, or respiratory manifestations—none of which are typically associated with MS. Emphasis is placed on recognizing these features in the context of a detailed patient history, examination, and targeted diagnostic testing. For each clinical scenario, the chapter provides a differential diagnostic framework and illustrative examples. By raising awareness of atypical features, this chapter aims to enhance diagnostic accuracy, guide further investigations, and support timely referral or treatment modifications in suspected MS cases.