Overview: In cats, the most serious of adverse effects following vaccination is the occurrence of invasive sarcomas (mostly fibrosarcomas): so-called ‘feline injection-site sarcomas’ (FISSs). These develop at sites of previous vaccination or injection. They have characteristics that are distinct from those of fibrosarcomas in other areas and behave more aggressively. The rate of metastasis ranges from 10–28%. Pathogenesis: The pathogenesis of these sarcomas is not yet definitively explained. However, chronic inflammatory reactions are considered the trigger for subsequent malignant transformation. Injections of long-acting drugs (such as glucocorticoids, and others) have been associated with sarcoma formation. Adjuvanted vaccines induce intense local inflammation and seem therefore to be particularly linked to the development of FISS. The risk is lower for modified-live and recombinant vaccines, but no vaccine is risk-free. Treatment and prevention: Aggressive, radical excision is required to avoid tumour recurrence. The prognosis improves if additional radiotherapy and/or immunotherapy (such as recombinant feline IL-2) are used. For prevention, administration of any irritating substance should be avoided. Vaccination should be performed as often as necessary, but as infrequently as possible. Non-adjuvanted, modified-live or recombinant vaccines should be selected in preference to adjuvanted vaccines. Injections should be given at sites at which surgery would likely lead to a complete cure; the interscapular region should generally be avoided. Post-vaccination monitoring should be performed.