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Purpose For many low- and middle-income countries (LMICs), breast cancer (BC) screening based on mammography is not a viable option. Clinical breast examination (CBE) may represent a pragmatic and cost-effective alternative. This paper examines the cost-effectiveness of CBE screening programme among a patient group for whom its cost-effectiveness is likely to be least evident (HER2-positive patients) and discuss the wider implications for BC screening in LMICs. Methods A Markov model was used to examine clinical and economic outcomes over a life-time horizon from the patient, public payer, and healthcare sector perspective. HER2-positive patients entered the model at either disease-free survival or metastatic BC state. The downstaging effect of CBE determined the starting probabilities in the no-screening and screening scenarios. The model used a monthly cycle length, with half-cycle correction. Costs and outcomes were discounted at 1.5% annually. Results Compared with no-screening, the cost-effectiveness ratio (ICER) per quality-adjusted life-year gained for the CBE screening programme was $1801, $2381, and $4179 from three mentioned perspectives, respectively. The finding of cost-effectiveness remained robust to a range of sensitivity analyses. The parameters to which ICERs are most sensitive are average age of cohorts, reduction in proportion of metastatic patients at diagnosis, cost of CBE, and BC detection rate of the programme. Conclusion For HER2-positive patients and compared with no-screening, CBE screening programme in Vietnam is cost-effective from all investigated perspectives. CBE is a ‘good value’ intervention and should be considered for implementation throughout Vietnam as well as in LMICs where mammography is not feasible.