Magnetic resonance imaging (MRI) is central to the diagnosis of multiple sclerosis (MS), but its limited specificity can result in diagnostic challenges, especially in atypical cases or when alternative pathologies exhibit overlapping imaging features. This chapter offers a comprehensive overview of MRI red flags that should prompt consideration of alternative diagnoses to MS. Key patterns and imaging features discussed include brain calcifications; conus and cauda medullaris pathology; diencephalic involvement and hypophysitis; dominant or isolated brainstem involvement; ischemic lesions; lesions resolution; leukodystrophy-like pattern; longitudinally extensive transverse myelitis (LETM); brain microhemorrhages; persistent or simultaneous contrast enhancement; and mass-like tumefactive lesions. Emphasis is placed on lesion morphology, symmetry, distribution, and temporal evolution, which help differentiate true demyelinating lesions from their mimics. The utility of specific MRI techniques such as diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), and contrast-enhanced sequences is addressed. Recognizing these imaging red flags is critical to avoid misdiagnosis, inappropriate treatment, and delays in identifying the correct etiology. This chapter provides clinicians and radiologists with a detailed diagnostic framework to interpret MRI findings in suspected MS cases with atypical features, enhancing diagnostic accuracy in complex neuroimaging scenarios.