Total cancer mortality rates in the European Union have declined by about 7% over the period 1982-2002. The aim of the present study was to investigate similar trends in Spain over the period 1975 to 2004 by age, sex, and cancer site.Trends in Spanish mortality rates (standardized to the world standard population) for all cancers and for 14 major cancer sites for the years 1975 to 2004 are analyzed. Join point regression analysis was used to identify points where a significant change in trend occurred.The overall cancer mortality rate in Spain in men and women declined by about 1% a year between 1995 and 2004. For the period 1975 to 2004, declines were observed for several neoplasms: lip, -3.62% in men and -3.39% in women; esophagus, -0.28% in men and -2.73% in women; stomach, -2.99% in men and -3.66% in women; liver, -0.52% in men and -3.77% in women. There was a substantial rise in: colon cancer, 3.72% in men and 1.79% in women; pancreas, 2.21% in men and 2.25% in women; lung cancer rose 1.18% in men and 0.97% in women, and between 1999-2004 it rose 5.23% in women. Most of these are tobacco-related neoplasms.Cancer mortality in Spain is mainly a tobacco-related problem. More attention needs to be focused on campaigns to decrease and prevent smoking, especially in the young, where smoking rates are higher than in the general population.