Genetic variants in hormone receptor genes may be crucial predisposing factors for breast cancer, and microsatellites in the estrogen receptor (ESR1, ESR2) and androgen receptor (AR) genes have been suggested to play a role. We studied 258 African-American (AA) women with breast cancer and 259 hospital-based controls, as well as 349 Nigerian (NG) female breast cancer patients and 296 community controls. Three microsatellites, ESR1_TA, ESR2_CA and AR_CAG, in the ESR1, ESR2 and AR genes, respectively, were genotyped. Their repeat lengths were then analyzed as continuous and dichotomous variables. Analyses of continuous variables showed no association with breast cancer risk in either AA or NG at ESR1_TA; AA cases had shorter repeats in the long allele of ESR2_CA than AA controls (Mann-Whitney P  = 0.036; logistic regression P  = 0.04, OR  = 0.91, 95% CI 0.83–1.00), whereas NG patients had longer repeats in the short allele than NG controls (Mann-Whitney P  = 0.0018; logistic regression P  = 0.04, OR  = 1.06, 95% CI 1.00–1.11); and AA cases carried longer repeats in the short allele of AR_CAG than AA controls (Mann-Whitney P  = 0.038; logistic regression P  = 0.03, OR  = 1.08, 95% CI 1.01–1.15). When allele sizes were categorized as dichotomous variables, we discovered that women with two long alleles of ESR2_CA had increased risk of breast cancer (OR  = 1.38, 95% CI 1.10–1.74; P  = 0.006). This is the first study to investigate these three microsatellites in hormonal receptor genes in relation to breast cancer risk in an indigenous African population. After adjusting for multiple-testing, our findings suggest that ESR2_CA is associated with breast cancer risk in Nigerian women, whereas ESR1_TA and AR_CAG seem to have no association with the disease among African American or Nigerian women.