We studied eight cases of the Rubinstein—Taybi syndrome to determine if a detectable chromosome change is associated with this syndrome. High resolution G‐banded analysis of prometaphase chromosomes was carried out on venous blood with two to four karyotypes analyzed for each patient. Initial study of two patients suggested an abnormality in chromosome 15q, but blinded analysis and review of the karyotypes proved to be normal. Therefore, all eight patients had normal G‐banded prometaphase chromosome studies. Because of technical difficulties and observer bias, we urge caution in using high resolution chromosome studies to screen whole karyotypes for suspected abnormal