A lack of information about American Indians' awareness and knowledge regarding the human papillomavirus (HPV) exists. This study conducted focus groups among American Indian college students in the Southwest to assess HPV awareness. Fifty-three students participated in the study. Grounded Theory analysis identified common themes. Females reported greater awareness, knowledge and perceived severity of HPV. Frequent misunderstandings about HPV were observed. Males, adolescents and young adults were recommended as intervention targets, with schools and healthcare visits as preferred avenues for education. Recommendations for developing and implementing culturally-competent HPV educational programs for American Indian adolescents and young adults are provided.