The aim of this study was to evaluate net survival from cancer diagnosed during the period 2001–2010 in the north region of Portugal to identify the tumours that need actions to improve the outcomes. Data were retrieved from the North Region Cancer Registry of Portugal database. The top 20 cancer sites in adults were considered: oesophagus, stomach, colon, rectum, pancreas, liver, larynx, lung, skin melanoma, breast, cervix, corpus uteri, ovary, prostate, kidney, bladder, brain and central nervous system, thyroid, non-Hodgkin lymphoma and multiple myeloma. Net survival was estimated using the Pohar–Perme estimator. The effect of diagnosis period was evaluated using flexible parametric models adjusted for age and sex where appropriate. Thyroid and prostate cancers presented the best 5-year survival (>90%), whereas oesophagus, pancreas, liver and lung cancers the worst 5-year survival (<20%). The largest increase in survival was observed for the larynx. A significant decrease in age-adjusted and sex-adjusted excess mortality was observed for stomach, colon, pancreas, larynx, melanoma, breast, brain and central nervous system, thyroid, non-Hodgkin lymphoma and multiple myeloma. For the other cancer sites, no significant trends were observed. For some of these sites, the downward trend in excess mortality was only observed in the short term. An important picture of population-based cancer survival outcomes for the first decade of the millennium in the north region of Portugal was presented in this study. It has been shown that improvements in survival were not universal for all cancer sites. These results should be used to highlight tumours where intervention is needed the most.