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Objectives: To review the similarities and differences between Solar Lentigines and Melasma, and present work investigating how molecular changes in skin underpin the presentation of these two conditions within and across populations. Introduction: Hyperpigmented conditions are common occurrences in skin across populations, & characterised by both visual and histological (changes to the skin’s underlying structure) changes. Two common conditions are Solar Lentigines and Melasma which, although they have similarities in visual presentation, have different prevalence across populations. We summarise the similarities and differences of these two hyperpigmentation conditions and outline how taking a Systems Biology approach can give new insights into the biological mechanism driving their appearance. Materials / method: We reviewed the literature for studies examining the prevalence of each condition within and across different populations. We examined 5 studies investigating molecular changes in these two conditions, specifically changes to gene activity (transcriptomics). We then took a Systems Biology approach to determine the main networks and pathways that are altered in each condition, and how such an approach can lead to new understanding of how different causal factors of each condition are driving a hyperpigmented state. Results: Solar lentigines are small round hyper-pigmented areas of skin which appear with advancing age and are linked to sun-exposure. Melasma, in contrast, is characterised by larger and more diffuse hyperpigmentation areas of skin that predominate in women, and notable during pregnancy. We also show how molecular investigations are starting to pinpoint where similarities between the two conditions underpin the similarity in appearance, whereas differences in the molecular changes are likely linked to the degree to which different causal factors drive the varying presence of each condition. Conclusion: Melasma and solar lentigo are both hyperpigmentation disorders and have similarities in the molecular changes which are linked to their hyperpigmented state. However, the different causal mechanisms driving variation in their prevalence in different populations are also captured in the molecular data. Further work to identify the key regulators of the molecular changes, particularly in the early development of each condition, should help pinpoint the key molecular drivers of said conditions and help explain why they vary by age and population.