The ITGAM Arg77His (rs1143679) and Ala858Val (rs1143683) polymorphisms have been found to be strong contributors to systemic lupus erythematosus (SLE) development. There are evident population distinctions in terms of SLE distribution and manifestations; therefore, we investigated the distribution of the ITGAM Arg77His and Ala858Val polymorphisms in patients with SLE (n = 154) and control subjects (n = 276) in a sample of the Polish population. We observed that patients with the ITGAM His/His and Arg/His genotypes displayed a 1.811-fold increased risk of SLE incidence (95% confidence intervals [95% CI] = 1.171-2.802, p = 0.0089). Odds ratio (OR) for the homozygous ITGAM His/His genotype was 7.333 (95% CI = 0.8119-66.241, p = 0.0576). We also found that the ITGAM 858Val variant might be a risk factor in the occurrence of SLE; the OR for this allele amounted to 1.458 (95% CI = 1.021-2.080, p = 0.0372). There was an association of the ITGAM His/His and Arg/His genotypes with the occurrence of arthritis OR = 3.486 (95% CI = 1.619-7.508, p = 0.0015). We also observed an association between the ITGAM His/His and Arg/His genotypes and renal symptoms in the course of SLE OR = 2.975 (95% CI = 1.478-5.988; p = 0.0023). Our findings confirmed that there is an association of the ITGAM 77His or 858Val variants with SLE incidence and some clinical manifestation of this autoimmune disorder.