Background: The anti-PD1 antibody (Ab) Nivolumab (Nivo) has demonstrated to improve the overall survival (OS) in patients (pts) with metastatic melanoma (MM) compared to DTIC. Pembrolizumab (Pembro), another anti-PD1, showed durable antitumor activity in pts with MM and has been approved in the US for the treatment (tmt) of MM that progressed on ipilimumab and, if BRAFV600 mutant, a BRAF inhibitor. To date, no lab test has been identified to predict clinical benefit (CB) to anti-PD1 Abs. Methods: This retrospective observational study included pts with MM who received anti-PD1 tmt in a single institution. The objective was to identify whether an increase of at least 100/mm3 at 3 weeks over the baseline or increase > 400/mm3 at 12 weeks in the absolute eosinophil counts (AEC) could predict CB. Blood tests were performed before every administration. Response to tmt according immune-related response criteria, progression free survival (PFS) and OS were evaluated. Descriptive statistics were used to analyze patient baseline characteristics. Response rates (RR) were compared by exact Fisher test. PFS and OS were estimated by the Kaplan-Meier method. Results: From March 2013 to December 2014, 29 pts were treated with anti-PD1 Abs (3 pts with Nivo and 26 pts with Pembro). Median age was 57 years (range 30-83) with 10.3% stage M1a, 24.1% M1b and 65.5% M1c, and 51.7% had elevated LDH. Pts who experienced an increase in AEC over the baseline > 100/mm3 at 3 weeks demonstrated better outcomes in terms of RR (55.6% vs 9.1%, p = 0.190), PFS (9.9 [95% CI: 5.8-14.0] vs 2.6 [95% CI: 1.0-4.2] months, p = 0.008) and OS (18.8 [95% CI: 15.5-22.1] vs 6.9 [95% CI: 3.5-10.3] months, p = 0.001) compared with those who did not. Moreover, pts with an AEC > 400/mm3 at 12 weeks responded to tmt (100% vs 18.2%, p = 0.002) and showed more benefit regarding PFS (18.6 vs 3.6 months, p < 0.0001) and OS (not reached vs 11.4 months, p = 0.017) compared to those who did not. Conclusions: An increase in AEC of 100/mm3 over baseline at week 3 and an absolute AEC > 400/mm3 at week 12 during anti-PD1 tmt might identify pts with MM most likely to experience long-term disease control with anti-PD1 Abs.