Background Clinical practice guidelines (CPGs) inform evidence-based decision-making in the clinical setting; however, systematic reviews (SRs) that inform these CPGs may vary in terms of reporting and methodological quality, which affects confidence in summary effect estimates. Objective Our objective was to appraise the methodological and reporting quality of the SRs used in CPGs for cutaneous melanoma and evaluate differences in these outcomes between Cochrane and non-Cochrane reviews. Methods We conducted a cross-sectional analysis by searching PubMed for cutaneous melanoma guidelines published between January 1, 2015, and May 21, 2021. Next, we extracted SRs composing these guidelines and appraised their reporting and methodological rigor using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) checklists. Lastly, we compared these outcomes between Cochrane and non-Cochrane SRs. All screening and data extraction occurred in a masked, duplicate fashion. Results Of the SRs appraised, the mean completion rate was 66.5% (SD 12.29%) for the PRISMA checklist and 44.5% (SD 21.05%) for AMSTAR. The majority of SRs (19/50, 53%) were of critically low methodological quality, with no SRs being appraised as high quality. There was a statistically significant association (P<.001) between AMSTAR and PRISMA checklists. Cochrane SRs had higher PRISMA mean completion rates and higher methodological quality than non-Cochrane SRs. Conclusions SRs supporting CPGs focused on the management of cutaneous melanoma vary in reporting and methodological quality, with the majority of SRs being of low quality. Increasing adherence to PRISMA and AMSTAR checklists will likely increase the quality of SRs, thereby increasing the level of evidence supporting cutaneous melanoma CPGs.