Disconcerting levels of misdiagnosis are common in point-of-care rapid HIV testing programmes in sub-Saharan Africa. To investigate potential pathways to misdiagnosis, we interviewed 28 HIV testers in Zimbabwe and conducted weeklong observations at four testing facilities. Approaching adherence to national HIV testing algorithms as a social and scripted practice, dependent on the integration of certain competences, materials and meanings, our thematic analysis revealed three underlying causes of misdiagnosis: One, a lack of confidence in using certain test-kits, coupled with changes in testing algorithms and inadequate training, fed uncertainties with some testing practices. Two, difficult work conditions, including high workloads and resource-depleted facilities, compounded these uncertainties, and meant testers got distracted or resorted to testing short-cuts. Three, power struggles between HIV testers, and specific client-tester encounters created social interactions that challenged the testing process. We conclude that these contexts contribute to deviances from official and recommended testing procedures, as well as testing and interpretation biases, which may explain cases of misdiagnoses. We caution against user-error explanations to misdiagnosis in the absence of a broader recognition of how broader structural determinants affect HIV testing practices.