Background: Adults living with HIV have an increased risk of malignancy yet there is a paucity of data for adolescents and young adults (AYA) with perinatally acquired HIV (PaHIV). Methods: Retrospective cohort analysis of all-cause mortality and malignancies in AYA with PaHIV aged 10-24 years attending a tertiary unit from 01 January 2004 to 31 December 2017, assessing cancer presentation, immunology and comparing mortality and malignancy incidence to age-matched UK general population rates. Results: A total of 290 AYA with PaHIV contributed 2644 person-years of follow up. Six (2.0%) died within the study period at a median age of 17 years (interquartile range [IQR]15-19), 3 of malignancy, 2 with end-stage HIV and 1 with cryptococcal meningitis. Overall mortality rate was 2.3/1000 person-years, with an age-matched general population rate of 0.2/1000 person-years. Eight (2.8%) were diagnosed with a malignancy; 6 with lymphoma (n=3 Hodgkin's, n=1 Burkitt's, n=2 B-cell) and one each with hepatocellular carcinoma and gastrointestinal adenocarcinoma. At cancer diagnosis the median age was 19 years (IQR 14-23), median CD4 T cell count was 453 cells/mm3 (IQR 231-645) and median length of HIV viremia was 15 years (IQR 12-17). The incidence rate of a malignancy was 3.0/1000 person-years in AYA with PaHIV, whilst that in the age-matched general population is 0.2/1000 person-years. Conclusion: AYA living with PaHIV had an increased risk of all-cause mortality and of malignancy compared to their uninfected peers, with the excess in malignancy driven by lymphomas. It is hoped that earlier access to antiretroviral therapy will mitigate some of the AIDS-defining and non-AIDS defining risks for future generations.