Previous studies have recommended no special precautions for radiation when handling sentinel node specimens in the pathology laboratory. We reviewed 7 years of data concerning radioactivity in 2,902 sentinel node and primary resection specimens received in our pathology laboratory. The percentage of specimens with greater than background radiation (> or =0.2 mrem/h) rose from 6.3% to 34.8% from 2003 to 2009 (P < .001); specimens with more than 10 mrem/h rose from 0.0% to 9.3% (P < .001). Four specimens were measured at 100 mrem/h. While mastectomy followed by skin excisions for melanoma were the most common specimens to have radiation more than 2.0 mrem/h (32.2% and 27.3%, respectively), this level of radiation was found in all types of cases examined. The radiation dose administered to individual patients for specimens with more than 30 mrem/h was significantly higher than a sample of specimens with less than 0.2 mrem/h (n = 25 each; median, 1.3 and 1.0 mCi, respectively; P = .02). While the higher level of radiation we found correlates with increasing administered dose of radiation, other factors may also have a role. Routine measurement of radioactivity for all sentinel node specimens in the pathology laboratory is recommended.