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To evaluate the Dutch-English Lambert-Eaton Myasthenic Syndrome (LEMS) Tumour Association Prediction (DELTA-P) score in a prospective cohort of patients with newly diagnosed LEMS to assess the clinical validity of this tool in a real-world setting. Clinical features from 87 patients with LEMS, occurring within three months from disease onset, were collated to produce a DELTA-P score for each patient. Lung cancer was detected in 44/87 (51%) LEMS patients. Weight loss ≥ 5%, tobacco use at LEMS onset and age at onset ≥ 50 years were independent predictors for the development of small-cell lung cancer (SCLC) in LEMS patients in multivariable analysis. Median DELTA-P scores were significantly higher in SCLC-LEMS patients (3.5, 95% CI 3 to 4) compared to non-tumour-LEMS (2, 95% CI 1 to 2) (P < 0.0001). Higher DELTA-P scores increased the risk of SCLC stepwise (score 0 = 0%, 1 = 18.8%, 2 = 45%, 3 = 55.5%, 4 = 85.7%, 5 = 87.5%, 6 = 100%). The area under the curve of the receiver operating curve was 82.5% (95% CI 73.9% to 91%). The DELTA-P cancer prediction score, calculated at the time of LEMS diagnosis, is an effective tool for cancer screening in an independent, prospective study setting.