The sigma-1 receptor (SIGMAR1) is a subtype of a nonopioid sigma receptor family and is implicated in numerous functions connected with Alzheimer's disease (AD). Two common genetic variants were identified in SIGMAR1: GC-241 -240TT and Q2P (A61C). It was suggested that the TT-C haplotype is a protective factor for AD. We decided to investigate a putative link between the variants of SIGMAR1 and AD in a group of Polish patients with late-onset AD, in patients with mild cognitive impairment, and in a control group. We observed no significant differences for the SIGMAR1 allele, genotype, haplotype, and diplotype distributions between the studied groups. Multivariate logistic regression analysis showed no interaction between the APOE4 and SIGMAR1 polymorphisms. Further studies using data from different populations are required to elucidate the effect of SIGMAR1 polymorphisms on AD.