Abstract Ultraviolet radiation (UVR) is the most common environmental carcinogen to cause cutaneous squamous cell carcinoma (cSCC). However, other carcinogens may also play a role and should be suspected when cSCC occurs in people with skin of colour (SOC) in whom ultraviolet (UV)-induced cSCC is less common. We present the case of a South Asian female who presented with an aggressive cSCC, which we hypothesize was related to previous arsenic exposure. A 70-year-old Bangladeshi woman (skin phototype V) presented with a 4-cm diameter, tender, keratotic plaque at the base of her left thumb, which had been present for 12 years and was slowly enlarging. There was no associated lymphadenopathy. She also had multiple palmoplantar keratotic papules and two hyperkeratotic plaques in UV-protected areas on her trunk. Histology of the lesion on her thumb confirmed a cSCC with high-risk features: poorly differentiated, invasion 9.5 mm into fibromuscular tissue, perineural invasion (nerve diameter > 0.1 mm) and vascular invasion. The truncal plaques were confirmed to be SCC in situ. The cSCC was incompletely excised and subsequently showed extensive involvement of periosteal soft tissues with invasion into bone marrow. Staging computed tomography showed no evidence of nodal or distant metastatic disease. She subsequently underwent ray amputation and remains under close clinical surveillance. Given the cSCC location and her skin phototype, potential non-UV radiation (UVR) causes were explored. In view of the palmoplantar keratotic papules and SCC in situ, chronic arsenic exposure was suspected. Further questioning revealed a history of drinking well water in a rural village in Bangladesh throughout childhood and early adulthood, although exposure had stopped > 40 years ago. Arsenic exposure from contaminated groundwater was therefore considered to be the most likely diagnosis. She was started on long-term chemoprevention with acitretin. Arsenic is a potent human carcinogen and a well-recognized cause of cSCC; the latency period may be 30–40 years. Most cases are likely to be in people exposed through environmental arsenic exposure, such as contaminated groundwater, with some cases of exposure to arsenic-containing traditional medicines also reported. Carcinogenic mechanisms are uncertain but may involve dysregulation of the Hippo signalling pathway. In summary, although the incidence of UVR-related cSCC is lower, this case highlights the importance of considering risk factors, other than UVR, in cSCC arising in people with SOC. Identifying relevant carcinogens may require a detailed travel, social and cultural history and, more importantly, an awareness of the non-UVR causes of cSCC.