Multiple system atrophy (MSA) is a heterogenous condition, presenting with core clinical features of autonomic dysfunction, parkinsonism, and/or cerebellar ataxia. The presence of alpha-synuclein glial cytoplasmic inclusion is the hallmark of MSA. It shares a common pathological origin with Parkinson's disease (PD) and Lewy body dementia (DLB) and they are collectively grouped as "synucleinopathies." The pathological synuclein protein is now well- recognized in skin biopsies of these patients. Besides the pathological findings, radiological investigation is a useful diagnostic tool. Brain MRI helps rule out other etiologies, and findings like the "Hot-cross bun" sign, "putaminal atrophy," and "infratentorial findings" can assist with the diagnosis of MSA. Cardiac MIBG scan, autonomic testing, urodynamic studies can help differentiate MSA from other conditions. Although diagnostic tools are available for MSA diagnosis, clarity is needed on when to use these tests. We suggest a diagnostic algorithm to navigate the use of these tests. However, this algorithm is not intended to replace the use of current MDS diagnostic criteria of MSA.