The laboratory workup of patients with pheochromocytoma and extra-adrenal paraganglioma (PPGLs) has traditionally focused on biochemical measurements of tumor secretory products or their metabolites, with ultimate diagnosis resting on routine histopathology and immunohistochemistry. While such testing remains important, the needs to distinguish potentially metastatic from benign tumors and to identify tumors with a hereditary basis have stimulated searches for additional means to stratify patients according to risk of metastasis or presence of a particular mutation. Biomarkers based on traditional biochemical tests, such as profiles of catecholamine metabolites and granin-derived peptides, provide utility for both purposes, while novel biomarkers are being identified by proteomic and transcriptomic studies, the latter including microRNA expression profiling. Histopathological scoring methods for predicting metastatic potential, such as the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), are limited by poor interobserver concordance, discrepant results between studies and incomplete knowledge of how scores relate to genotype. Immunohistochemical staining for succinate dehydrogenase (SDH) subunit B to triage patients for genetic testing of SDH subunit genes illustrates the growing importance of pathology as an adjunct to genetic testing for disease stratification. Although considerable effort has been expended on microarray-based platforms to identify biomarkers of malignancy, as yet, none of those proposed have been demonstrated to reliably discriminate malignant from benign disease any better than the PASS. Because of the heterogeneity of PPGLs and variable time between first appearance of tumors and identification of metastases, any prospective study to establish prognostic efficacy requires large numbers of patients and extended follow-up.