The evaluation of a biochemical or hematological quantity measured in
a study group of employees during occupational health assessments invo
lves a comparison with a reference sample group. Part of this evaluati
on consists of checking whether the percentage of values larger than a
predetermined upper reference limit is significantly larger than the
percentage normally expected (2.5%, if the 97.5 percentile is used as
the upper reference limit). The reference limit, however, is estimated
from a random reference sample, the size of which, for many reasons,
may be relatively small; as a consequence, the reference limit estimat
e will be imprecise. In situations in which the reference sample size
is smaller than or not much larger than the study sample size, this im
precision results in the usual binomial test of significance being hig
hly inappropriate. We provide an exact nonparametric test valid for ai
l reference sample sizes.