The current landscape of cancer biomarkers is changing rapidly, with new and exciting developments. With the advances of proteomic technologies, many potential cancer biomarkers have been discovered. However, the number of new cancer biomarkers cleared or approved by the US FDA is rather limited. Although technological advances are important, clearly defining intended use, good study design and appropriate patient specimens are critical for the success of FDA approval. While obtaining FDA clearance/approval for newly developed and clinically useful cancer biomarkers has been slow, the reward for patient care could be enormous.