Targeted therapies for cutaneous melanoma, such as those based on specific BRAF inhibitors, have improved the treatment and enhanced the survival rate of patients who harbor the V600E point mutation in the BRAF gene. However, tissue biopsies to characterize BRAF mutation status are prone to sampling bias, due to the intrinsic heterogeneity of a tumor mass. In contrast, blood biopsies, which analyze circulating tumor DNA (ctDNA), offer the most complete and sensitive characterization of the mutation status of a tumor, provide early and more accurate diagnosis, but they require instrumental and costly molecular tests. Therefore, the development of low-cost but highly sensitive tests for the non-invasive identification of BRAFV600E mutation in ctDNA would be of great clinical utility as a routine screening for the early identification of responsive patients and the follow-up of targeted therapy's response. The present work developed a naked-eye, inexpensive, yet very specific colorimetric assay, whose sensitivity is suitable for the detection of BRAFV600E rare mutation in ctDNA. Such test potentially may detect at an early stage the mutation in the tumor mass, when the first mutated cells appear in the blood, by using minimal instrumentation and thus enabling its widespread implementation in the clinics, even in local, minimally equipped laboratories. Indeed, the test detects 0.5% of BRAFV600E in an excess of BRAFWT DNA, which matches the sensitivity of some commercial instrumental assays. Such sensitivity is thus clinically relevant for diagnostic purposes, allowing the early identification of drug-sensitive patients.