Adolescents undergoing treatment for cancer rate fatigue as their most prevalent and intense cancer- and treatment-related effect. Parents and staff rate it similarly. Despite its reported prevalence, intensity, and distressing effects, cancer-related fatigue in adolescents is not routinely assessed during or after cancer treatment. We contend that the insufficient clinical attention is primarily due to the lack of a reliable and valid self-report instrument with which adolescent cancer-related fatigue can be measured. Our aim was to determine the reliability and construct validity of a new instrument and its ability to measure change in fatigue over time. Initial testing involved 64 adolescents undergoing curative treatment of cancer who completed the Fatigue Scale-Adolescent (FS-A) at two to four key points in treatment in one of four studies. Internal consistency estimates ranged from 0.67 to 0.95. Validity estimates involving the FS-A with the parent version ranged from 0.13 to 0.76; estimates involving the staff version and the Reynolds Depression Scale were 0.27 and 0.87, respectively. Additional validity findings included significant fatigue differences between anemic and nonanemic patients (P=0.042) and the emergence of four factors in an exploratory factor analysis. Findings further indicate that the FS-A can be used to measure change over time (t=2.55, P<0.01). In summary, the FS-A has moderate to strong reliability and impressive validity coefficients for a new research instrument.