A 73-year-old Hispanic male smoker with biochemically recurrent, non-metastatic castration-sensitive prostate cancer (PC), well-controlled on androgen deprivation therapy (ADT), was found on longitudinal ctDNA monitoring to have acquired somatic DNA variants that had not been reported in his PC tissue, including a FGFR3-TACC3 gene fusion, raising suspicion for a second malignancy. Here, FGFR3 is linked to pachyonychia congenita.