INTRODUCTION: Many studies have reported the importance of the human microbiome in relationship to the overall health of its host. While recent studies have explored the microbiome's role in various types of cancer compared to healthy patients, this pilot study is the first to investigate differences in the skin microbiome composition among pancreatic adenocarcinoma patients, individuals with other cancers, and cancer-free controls. METHODS: The study characterizes the skin microbiome's potential associations with cancer status by analyzing skin swabs from the forehead and cheek of 58 participants using Next Generation Sequencing (NGS), differential abundance analysis, and machine learning techniques. RESULTS: The study results indicated that the cancer group displayed a significantly higher mean alpha diversity compared to the control group. Additionally, a machine learning classification model achieved a mean F1 Score of 0.943 in predicting cancer status, indicating measurable differentiation in the skin microbiome between the study groups. This differentiation is supported by differential abundance methods, including ANCOM-BC and MaAsLin2. DISCUSSION: This pilot study suggests that skin microbiome profiling could serve as a non-invasive biomarker for cancer detection and monitoring, which warrants a larger, longitudinal study to validate these results.