Bioinformatics, merging biological data with computer science, is increasingly incorporated into school curricula at all levels. This case study of 10 secondary school students highlights student individual differences (especially the way they processed information and integrated procedural and analytical thought) and summarizes a variety of critical situations that teachers may encounter when teaching bioinformatics. Students who integrated factual information with procedural and analytical skills were closest to content mastery; while students who had fundamental deficiencies in factual recall or were less adept in integrating higher order knowledge with specific facts and procedural skills had difficulty mobilizing critical analytical skills needed to master the bioinformatics tasks. Broader implications are presented for teacher education, curriculum design, and research.