Background: Except for testicular cancer and Hodgkin's disease, baseline data on semen quality in case of cancers as well as systemic pathologies of the young adult are scarce or based on low sample size. Methods: Semen quality in patients having testicular cancer (TGCT, n = 2315), Hodgkin's disease (HD, n = 1175), non-Hodgkin's lymphoma (NHL, n = 439), leukemia (L, n = 360), sarcoma (S, n = 208), brain tumour (BT, n = 40), Behcet's disease (Behcet's, n = 68) or multiple sclerosis (MS, n = 73) was studied and compared to that of 1448 fertile men candidates for sperm donation (CSD) and 208 partners of pregnant women (PPW). All samples were studied following the same methodology in a single laboratory. Post freezing and thawing semen characteristics were also studied. Results: The percentage of normozoospermic men was only 37 % for L patients and lower than 60 % for TGCT, NHL, S and BT. The level of sperm production was differently decreased according to pathologies, the median total sperm count in TC and L patients being four times lower (p < 0.01 when compared to CSD and PPW). The lowest percentage of progressively motile spermatozoa was found for L and BT patients (both, p < 0.01 compared to CSD and PPW). The percentage of morphologically normal spermatozoa was also reduced in cancer patients, especially in BT patients. Progressive motility after thawing in patients was about half that observed among candidates for sperm donation. In almost half of the semen of patients with testicular cancer or leukemia, the total number of motile spermatozoa per straw was less than 0.5 × 10 6 compared to 4.3 × 10 6 in CSD. Conclusions: The present data confirm on large series the deleterious impact of various cancers of the young adult on semen quality, establishing thus baseline data for future studies. Owing to the post-thaw quality of the frozen straws, future fertility projects for the majority of the patients studied (in case there is no post-treatment recovery of spermatogenesis) should necessitate an ICSI to provide the best chance of paternity whatever the fertility checkup in the female partner.