The primary progressive form of multiple sclerosis is characterised by a systematic increase in disability from the onset of the disease, usually without overlapping relapses. It is estimated that it accounts for 10–15% of all cases of multiple sclerosis, occurs with similar frequency in both sexes, and its symptoms appear at an older age, usually after 40. The initial manifestation usually consists of pyramidal symptoms and myelopathy. The most typical symptoms include progressive gait and sphincter function impairment. Symptoms of cerebellar syndrome, truncal syndromes, as well as visual and cognitive disturbances are less common. The clinical course with characteristic symptomatology resulting from the location of the changes primarily in the spinal cord, followed by the occurrence of initial symptoms, means that this form of multiple sclerosis requires careful differential diagnosis. It should be differentiated primarily from diseases causing lower limb paresis (myelopathy associated with vitamin B₁₂ deficiency, amyotrophic lateral sclerosis, spinal cerebellar ataxia, neuromyelitis optica spectrum disorder, Wernicke’s encephalopathy, Lyme disease, and spinal cord tumours). The diagnosis of primary progressive multiple sclerosis should be guided by the current 2017 McDonald diagnostic criteria. Understanding these criteria and being aware of the differences from the most common relapsing-remitting form of multiple sclerosis can be helpful in speeding up the diagnosis and implementing effective treatment. Even though new treatment options have emerged in recent years, primary progressive multiple sclerosis is still little known and too rarely recognised.