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The scientific community accepts that the total number of reported smallpox cases is just a fraction of the actual number of smallpox cases in any given year. The World Health Organization (WHO) was not established by the United Nations until 1948, and did not launch their campaign to eradicate smallpox until 1967; prior to this, there was no organization responsible for collecting or correlating data relating to smallpox (or any other disease for that matter). The WHO estimates that there were approximately 50 million cases of smallpox each year in the early 1950s, while the total number of reported cases fell below 100,000 in 1953. When the WHO launched their intensified plan to eradicate smallpox in 1967, they estimate that there were between 10 and 15 million cases worldwide, although only 132,000 cases were reported in this year. For these reasons, data for reported cases should only be used to highlight trends and the distribution of outbreaks across the globe; this should also be met with some scrutiny however, as the data suggests there was a minimal number of cases in South Asia in the early-1920s, before jumping above 200,000 cases in the late 1920s.

Europe, Central Asia and North America

The most reliable data comes from Europe, Central Asia and North America. The number of cases in Europe and Central Asia fell from over 173,000 in 1920 to as low as 700 in 1937; apart from a brief outbreak during the Second World War, these numbers remained low until the disease's eradication. For North America, the number of cases fell significantly between 1920 and 1940, however a number of epidemics did break out between these years, which caused the decline to fluctuate. The majority of countries in Europe, North America and Oceania (where cases were rare) reported their final cases of smallpox by the middle of the century, before the WHO launched their campaign.

The developing world

Data for other continents is scarce, due to a combination of technological, economic and administrative limitations, however the largest concentration of cases was observed on the Indian sub-continent throughout most of the twentieth century. There were a few spikes in smallpox cases in East Asia from the mid-1940s to the mid-1960s; these years coincide with the end of the Sino-Japanese and Chinese Civil Wars, and Mao's failed Great Leap Forward, however any connection is purely speculative. The numbers of smallpox cases on other continents were much lower throughout these years, although cases did persist until the 1970s. The final naturally-occurring case of the deadly variola major strain of smallpox was observed in Bangladesh in 1975, while the last naturally occurring case of the milder variola minor strain was observed in Somalia in 1977. The WHO spent the next two years verifying the eradication of naturally occurring smallpox across the globe, before the World Health Assembly finally declared it eradicated on May 8, 1980.