© 2015 Perrella et al. Background: Nipple pain is associated with early cessation of breastfeeding and may be caused by high intra-oral vacuum. However identification of high intra-oral vacuum is typically restricted to the research setting. This is the first reported case of an infant with high intra-oral vacuum that was clinically identified through a specific pattern of nipple trauma associated with nipple shield use. Knowledge of clinical signs associated with high intra-oral vacuum may facilitate early recognition of this unusual breastfeeding challenge. Case presentation: The mother of an exclusively breastfed 3 month old infant had severe bilateral nipple pain with minimal trauma that persisted from birth. The nipples were not misshapen immediately after breastfeeding and adjustments to infant attachment at the breast did not attenuate the pain. Examination of the infant's oral anatomy was unremarkable with no ankyloglossia present. Microbiological cultures of nipple swabs and breast milk were negative for bacterial and fungal growth, and prescribed antimicrobial treatments did not reduce the nipple pain. Mild blanching and erythema of the nipples were occasionally observed, and were not consistent with nipple vasospasm. Nipple shields were used regularly as they modified the pain, although this resulted in blisters that corresponded with the nipple shield holes. Measurement of infant intra-oral vacuum during breastfeeding confirmed intra-oral vacuum up to 307% higher than reference values. Breastfeeding gradually became less painful, and after 6 months was completely comfortable. Conclusions: High intra-oral vacuum is difficult to assess in the clinical setting and is likely an under-reported cause of early weaning that is not well understood. This original case report highlights high intra-oral vacuum as at differential diagnosis to be considered by health professionals when evaluating mothers experiencing strong nipple pain during the initiation of breastfeeding. A clinical screening tool is needed to enable prompt identification of these infants.