The aim of the study was to assess recent changes in lung cancer incidence and mortality trends in the male and female population in Southeastern Serbia, in the period 1999-2008. Data used for analyses were provided by the Cancer Registry of the Institute for Public Health, Nis. Incidence and mortality trends were based on crude and age-standardized incidence and mortality rates for the period 1999-2008. Standardized rates were calculated by the direct method of standardization (per 100,000), using the world population as the standard. Statistical significance was checked on the basis of correlation coefficient (r) for probability (p) on the level of 0.05. A total of 3,128 new cases and 2,327 deaths from lung cancer were registered (males/females ratio is 4:1). In males, the crude (107.94) and the age-standardized incidence rate (59.88) were four-fold higher than in females (27.10 and 14.21). In males, the crude mortality rate was four-fold higher than in females (80.61 vs. 19.87), while the age-standardized mortality rate was four and a half higher than in females (43.78 vs. 9.54). Lung cancer incidence trend, based on crude and age-standardized incidence rates, in females was increasing while in males was decreasing. Lung cancer mortality trends, based on crude and age-standardized incidence rates, were increasing in both sexes. Registration of unfavourable incidence and mortality trends of lung cancer indicate failure in primary and secondary prevention in the past. It is thus of vital importance to provide much intensive and comprehensive activities for primary and secondary prevention of lung cancer in the future, including education and rigorous tobacco control as well.