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Summary: Background: Skin self-examinations supplemented with mobile teledermoscopy might improve early detection of skin cancers compared with naked-eye skin self-examinations. We aimed to assess whether mobile teledermoscopy-enhanced skin self-examination can improve sensitivity and specificity of self-detection of skin cancers when compared with naked-eye skin self-examination. Methods: This randomised, controlled trial was done in Brisbane (QLD, Australia). Eligible participants (aged ≥18 years) had at least two skin cancer risk factors as self-reported in the eligibility survey and had to own or have access to an iPhone compatible with a dermatoscope attachment (iPhone versions 5–8). Participants were randomly assigned (1:1), via a computer-generated randomisation procedure, to the intervention group (mobile dermoscopy-enhanced self-skin examination) or the control group (naked-eye skin self-examination). Control group and intervention group participants received web-based instructions on how to complete a whole body skin self-examination. All participants completed skin examinations at baseline, 1 month, and 2 months; intervention group participants submitted photographs of suspicious lesions to a dermatologist for telediagnosis after each skin examination and control group participants noted lesions on a body chart that was sent to the research team after each skin examination. All participants had an in-person whole-body clinical skin examination within 3 months of their last skin self-examination. Primary outcomes were sensitivity and specificity of skin self-examination, patient selection of clinically atypical lesions suspicious for melanoma or keratinocyte skin cancers (body sites examined, number of lesions photographed, types of lesions, and lesions missed), and diagnostic concordance of telediagnosis versus in-person whole-body clinical skin examination diagnosis. All primary outcomes were analysed in the modified intention-to-treat population, which included all patients who had a clinical skin examination within 3 months of their last skin self-examination. This trial was registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12616000989448. Findings: Between March 6, 2017, and June 7, 2018, 234 participants consented to enrol in the study, of whom 116 (50%) were assigned to the intervention group and 118 (50%) were assigned to the control group. 199 participants (98 participants in the intervention group and 101 participants in the control group) attended the clinical skin examination and thus were eligible for analyses. Participants in the intervention group submitted 615 lesions (median 6·0 per person; range 1–24) for telediagnosis and participants in the control group identified and recorded 673 lesions (median 6·0 per person; range 1–16). At the lesion level, sensitivity for lesions clinically suspicious for skin cancer was 75% (95% CI 63–84) in the intervention group and 88% (95% CI 80–91) in the control group (p=0·04). Specificity was 87% (95% CI 85–90) in the intervention group and 89% (95% CI 87–91) in the control group (p=0·42). At the individual level, the intervention group had a sensitivity of 87% (95% CI 76–99) compared with 97% (95% CI 91–100) in the control group (p=0·26), and a specificity of 95% (95% CI 90–100) compared with 96% (95% CI 91–100) in the control group. The overall diagnostic concordance between the telediagnosis and in-person clinical skin examination was 88%. Interpretation: The use of mobile teledermoscopy did not increase sensitivity for the detection of skin cancers compared with naked-eye skin self-examination; thus, further evidence is necessary for inclusion of skin self-examination technology for public health benefit. Funding: National Health and Medical Research Council (Australia).