This article reports the diagnostic process for two patients with amyotrophic lateral sclerosis-parkinsonism (ALS-PS) in Guangdong Provincial People's Hospital, and analyzes the clinical features, incidence, prognosis, and possible pathogenesis of amyotrophic lateral sclerosis-plus syndrome (ALS-Plus) through literature review. Case 1 presented with parkinsonism of bradykinesia and lead-pipe rigidity, with a negative levodopa challenge test and without hyposmia and dementia; we considered this case as undifferentiated ALS-PS. Case 2 showed the clinical manifestations of bradykinesia and lead-pipe rigidity, as well as cerebellar and autonomic dysfunction, which could be attributed to a diagnosis of multiple system atrophy (MSA), and therefore, we considered this case as ALS-MSA. Among all patients with ALS, those with ALS-Plus accounted for approximately 13.6% and tended to have a shorter survival time than the patients with ALS alone. Related studies have tried to give a reasonable explanation for ALS-Plus, but the pathogenesis of this remains unclear, and further studies are needed for clarification. ALS-Plus is not rare in ALS, but it is easily neglected in clinical practice, as the damage to other systems, particularly the extrapyramidal system, in ALS-Plus is often covered by severe muscle atrophy and muscle weakness, and the neurologists still have no sufficient knowledge of ALS-Plus. Therefore, the awareness of this disease should be improved among neurologists, and detailed medical history and physical examination can help to avoid misdiagnosis and missed diagnosis.