We found that ZNF154 hypermethylation occurs in tissue samples from patients with early-stage tumors in 10 different cancer types; is not meaningfully associated with age or sex, or elevated in non-cancer conditions; and displays promising performance when used to classify plasma samples as tumor versus healthy donor controls, with AUCs of 0.85 for late-stage ovarian cancer, and 0.85 or 0.87 for late- or early-stage pancreatic cancer. Here, ZNF154 is linked to pancreatic neoplasm.