This report details almost 3 decades experience of the London epidermolysis bullosa (EB) reference centres of cutaneous squamous cell carcinomas (SCCs). The case series of 221 primary tumours from 44 individuals reiterates that this is a complication seen not just in severe recessive dystro­phic EB (RDEB-S), but also in other EB subtypes, albeit at a later age, highlighting the need for awareness and surveillance. Most individuals developed multiple SCCs with a tendency for aggressive behaviour, despite surgical excision. The median survival of just 2.4 years after diagnosis of initial SCC in RDEB-S is lower than in previously reported smaller series, and points to the need for more effective thera­pies. Although conventional treatments such as chemotherapy or radiotherapy appear generally limited in terms of survival benefit, newer targeted therapies such as cemiplimab may hold some potential.