Subtle neuropsychological deficits have been described in patients affected by amyotrophic lateral sclerosis (ALS) without dementia. Overall, selective impairment in memory function has been reported, but the source of memory impairment in ALS has yet to be defined. We performed neuropsychological screening in 20 ALS patients. Semantic encoding and post-encoding cue effects on the retrieval of word lists were investigated in the ALS patients and normal controls. Severity of memory impairment was correlated to cerebral blood perfusion detected by single photon emission computed tomography (SPECT). ALS patients showed moderate impairments in frontal and memory tests. Short-term memory was normal, while serial position retrieval of word lists with normal recency effect but poor primacy effect showed long-term memory deficit. ALS patients performed better in cued encoding than in cued post-encoding recall condition. In the cued post-encoding condition, the primacy effect in word list recall improved significantly in controls, but not in ALS patients, as compared with both the free recall and cued encoding conditions. SPECT hypoperfusion was observed in frontal and temporal areas in ALS patients. ALS patients showed a long-term memory deficit which did not improve in cued post-encoding condition as it does for controls. We hypothesize abnormal retrieval processes related to frontal lobe dysfunction which entails difficulties in generating stable long-memory traces at encoding.