Abstract: The methods provided herein relate to the identification of novel DNA biomarkers and the use of the aberrant methylation patterns of the DNA biomarkers to diagnose small cell lung cancer (SCLC). Such methods may include diagnosing SCLC when there is an increase in methylation of one or more DNA biomarkers in a test sample compared with that in a normal sample. DNA methylation patterns of DNA biomarkers on a genome-wide scale may be determined using a variety of methods including the methylated-CpG island recovery assay (MIRA). In some embodiments, methods of treating a subject for SCLC or monitoring the treatment are also provided. Methods may include measuring the methylation levels of one or a combination of DNA biomarkers and administering chemotherapy to a subject when there is an increase in the methylation levels of the test sample in relation to that of the normal sample or standard sample.