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Skin cancer accounts for more cancer diagnoses in Australia than any other and of these, keratinocyte cancer (KC) make up the vast majority. Within NMSC carcinomas, cutaneous squamous cell carcinoma (SCC) has an annual incidence of 387/100,000 PY (person year). The work described in this thesis aims to depict these causes by studying a cohort of up to 172 adults, with early-onset SCC (diagnosis before 50 years), 74 sibling controls and 79 unrelated (partner) controls. Analyses were conducted of exposures to beta papillomaviruses (betaPV), of histopathological features, and of genetic variants associated with SCC. First, betaPV exposures in both past (serology) and present (DNA) were analysed for 15 betaPV types in cases, sibling, and partner controls. No definitive associations with early-onset SCC were identified. However, there was higher prevalence in cases, compared with sibling controls, of serologically detected exposure to multiple (> 3) increased risk betaPV subtypes. Second, histopathological features including stage, site, associated lesions, and tumour differentiation were analysed after pathological review. There were significant differences in body site, associated lesions and histological differentiation when compared. Tumours were more likely to have worse histologic stage if there was an associated benign lesion. Third, case-control analyses were conducted of 28 genetic loci, previously reported to be associated with skin cancer. Three quarters of the loci replicated associations in this early-onset cohort, suggesting that the overall genetic profile of individuals susceptible to early-onset SCC is like that of SCC. Three further loci, not detected in previous studies of SCC, were identified as potential novel associations. These data suggest that a continued focus on early-onset disease is likely to yield insights into preventable risk factors, surveillance, and clinically relevant management issues for younger adults at risk of this skin cancer.