Introduction The prevalence of cancer survivors increases though in the workforce. The issue of their return-to-work represents an important matter for their quality of life, but also a great challenge for the social security systems. Disease-specific return-to-work rates, broken down by groups are scarcely documented. This population-based cohort study aims at quantifying the return-to-work of Belgian workers and at identifying the determining factors. Methods We requested data from the Belgian Cancer Registry, the Inter Mutuality Agency and the Crossroad Bank for Social Security. We included all socially insured Belgian workers diagnosed between 2004 and 2011 with colorectal, breast, head & neck, prostate, testis, lung and corpus uteri cancer and who were active on the labor market at diagnosis. The end of (administrative) follow-up was 31st December 2012. After having solved legal, ethical and technical issues for the coupling, we performed group-based modeling for longitudinal data using the ‘proc traj’ package in SAS. We included demographic, health-related and work-related factors in the analysis and observed how these factors interplay to determine the working status. Results Among the 38,930 workers with cancer included, after 5 years follow-up, 18% died, 69% were (partially) active, 5% were unemployed and 2% were disabled. The group-based modeling revealed the existence of 3 types of work trajectories: working probabilities being high and stable during the whole follow-up; or low and stable or decreasing in the first 2 years and then increasing. Different trajectories appear according to the follow-up time: after 3 years of follow-up, eight groups of individuals emerged, of which four have between 70% and 100% of their workers being active. After 4 years, 3 on the 9 groups have more than 80% of their workers being active; and after 5 years, 3 groups on 10 have more than 80% of the workers being active. Among the workers comprise on these groups, we mainly find women with breast cancer; men with prostate cancer and workers aged 36–50 years old. Conclusion The results of our study reported that workers with cancer who resumed work were mainly self- employed and middle-age workers (36–50) with testis or breast cancers. Lung and prostate were negatively associated with the RTW and young workers seem to be at-risk of unemployment. It suggests that an early assessment of the worker's profile would allow the identification of those who would require support in order to prevent their exclusion from the labour market.