Abstract: Changing adolescents’ sun protection behaviors remains a challenge, and the need for effective interventions targeting this group is a priority, particularly in warmer climates where emphasis on appropriate sun protection remains a year-round concern. However, there has been little prospective research on the effect of school-based sun protection interventions, particularly on adolescents, especially teens aged 15 to 18. High school science students in Palm Beach County, Florida, received a seven-lesson sun protection and early detection curriculum preceded by pretests and followed with post-tests 6 months later. The main outcome measures were student knowledge and sun protection practices, including adherence to sunscreen recommendations. Of 344 students completing the baseline surveys, 184 students completed the postintervention questionnaire. Overall, there were significant improvements from baseline to follow-up for many of the knowledge questions. Greatest change scores were seen in the children's ability to correctly define the five rules of early detection of skin cancer (27–60%, p < 0.001) with improved change scores by gender and race persisting after 6 months. No significant differences were found in reported use of sunscreen, hat wearing, or sunglasses, although there was a slight decrease in the reported use of always wearing sun protective clothing (p = 0.03). In conclusion, in this study, a skin cancer prevention and detection curriculum integrated into high school biology, resulted in knowledge gains maintained at least 6 months after classroom teaching. For example, procedural knowledge (e.g., knowing ways to identify early malignant moles) obtained in this study improved in 6 months, and may lay the foundation for future behavioral change. Sun protection activities in the United States have met with many challenges and obstacles and thus, further work is needed to better understand what combination of knowledge-based information, activity-based education, school-wide changes, and community efforts, will create a long-term systemic improvement in sun protection habits in children.