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A rapid aneuploid screen using fluorescence <jats:italic>in situ<\/jats:italic> hybridisation on uncultured amniotic fluid cells revealed 3 signals for chromosome 21, consistent with trisomy 21. <jats:italic>In situ<\/jats:italic> metaphase cultures revealed a 46,XY normal male karyotype. These discordant results may be explained by a sub\u2010standard batch of the commercially available probe or alternatively, a very specific variation within the sample interacting with the probe. Alternative strategies are proposed in order to safeguard against inappropriate clinical action as a consequence of discordant results. 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