Tropical dry forests are biologically important biomes sustaining a high rate of endemic species. However, these forests are highly threatened by human activities that negatively impact them on distinct levels, including the genetic diversity. Within the framework of landscape genetics (that seeks to evaluate the relation of characteristics of the environmental matrix with population genetics), we used ISSR markers to evaluate the relationship between the alteration of tropical dry forest by human-induced activities (conserved vs. disturbed) with the genetic structure of four breeding sites of the southern pygmy mouse Baiomys musculus. Averaging among the 105 loci used, the unbiased heterozygosis per population (0.247-0.305) was statistically similar among the four sites, as well as between conserved and disturbed conditions (2-way ANOVA F ((3,16)) = 1.47, P = 0.1984). The genetic differentiation among the four breeding sites was high (F (ST) = 0.1122; 95 % CI 0.082-0.146) considering the geographical scale evaluated (ca. 4 km). Both, a factorial correspondence analysis and a model-based clustering analysis showed the existence of four genetic groups (one per breeding site). However, no association of genetic structure with disturbance conditions was revealed by these analyses. The absence of differences in mean genetic diversity and the lack of association of genetic structure with habitat transformation suggest that B. musculus has enough behavioral plasticity and enough genetic diversity to respond to environmental heterogeneity caused by human activities. We discussed conditions in which habitat transformation could indeed favor B. musculus.