Women in the United States have among the highest incidence rates of breast cancer. The reasons behind this are not fully understood. In this study we analyzed US ecological data to examine the effect of ambient air pollution on breast cancer incidence. Time trends and regional variations in breast cancer incidence were assessed in relation to emissions of air pollutants. A statistically significant increase in the incidence of female breast cancer in US was observed during 1986-2002, which could occur following the increased emissions of air pollutants as a result of industrial development and automobile use. Emissions of nitrogen oxides, carbon monoxide, sulfur dioxide, and volatile organic compounds were shown to be positively associated with breast cancer incidence with r = 0.89, 0.82, 0.71, and 0.68, respectively (p < 0.001). A higher incidence rate of breast cancer was found in high emission regions and metropolitan areas. This study suggests a possible association between air pollution and female breast cancer in US.