Breast cancer is the most common cancer in women worldwide. The analysis of breast cancer mortality is needed to plan healthcare systems. This study aims to evaluate the age-period-cohort effects on breast cancer mortality in Andalusia (Southern Spain) as a whole and in each of its eight provinces during the period 1981-2008. A population-based ecological study was conducted. In all, 19,707 deaths from breast cancer were analysed for individuals between the ages of 40 and 84 years who died in Andalusia in the period of study. A nonlinear regression model was estimated for each gender group and geographical area. The effects of age, year of death and birth cohort were parameterised using B-spline smoothing functions. There is an upward trend in mortality by age until around the age of 75 years, from which point the trend turned downwards. The analysis of the cohort effect reveals a steady fall in breast cancer mortality risk for female generations born after 1940. Death rates increased until 1995 and then declined until the end of the period. There is an age-period-cohort effect on breast cancer mortality similar in all the provinces of Andalusia and for Andalusia as a whole. If the current trends continue, it can be expected that these effects will continue to reduce female mortality.